Treatment. Most hyphaemas absorb spontaneously and thus need no treatment. Sometimes hyphaema may be large and associated with rise in IOP. In such cases, IOP should be lowered by acetazolamide and hyperosmotic agents. If the blood does not get absorbed in a week’s time, then a paracentesis should be done to drain the blood. 2. Iris prolapse. It is usually caused by inadequate suturing of the incision after ICCE and conventional ECCE and occurs during first or second postoperative day. This complication is not known with manual SICS and phacoemulsification technique. Management.A small prolapse of less than 24 hours duration may be reposited back and wound sutured. A large prolapse of long duration needs abscission and suturing of wound. 3. Striate keratopathy. Characterised by mild corneal oedema with Descemet’s folds is a common complication observed during immediate postoperative period. This occurs due to endothelial damage during surgery. Management. Mild striate keratopathy usually disappears spontaneously within a week. Moderate to severe keratopathy may be treated by instillation of hypertonic saline drops (5% sodium chloride) along with steroids. 4. Flat (shallow or nonformed) anterior chamber. It has become a relatively rare complication due to improved wound closure. It may occur due to wound leak, ciliochoroidal detachment or pupil block. i. Flatanteriorchamberwithwoundleakis associated with hypotony. It is diagnosed by Seidel’s test. In this test, a drop of fluorescein is instilled into the lower fornix and patient is asked to blink to spread the dye evenly. The incision is then examined with slit-lamp using cobalt-blue filter. At the site of leakage, fluorescein will be diluted by aqueous. In most cases wound leak is cured within 4 days with pressure bandage and oral acetazolamide. If the condition persists, injection of air in the anterior chamber and resuturing of the leaking wound should be carried out. ii. Ciliochoroidal detachment. It may or may not be associated with wound leak. Detached ciliochoroid presents as a convex brownish mass in the involved quadrant with shallow anterior chamber. In most cases, choroidal detachment is cured within 4 days with pressure bandage and use of oral acetazolamide. If the condition persists, suprachoroidal drainage with injection of air in the anterior chamber is indicated. iii.Pupilblockduetovitreousbulge(after ICCE or due to adhesions with IOL more common with ACIOLs) leads to formation of iris bombe and shallowing of anterior chamber. If the condition persists for 5–7 days, permanent peripheral anterior synechiae (PAS) may be formed leading to secondary angle closure glaucoma. • Pupil block is managed initially with mydriatic, hyperosmotic agents (e.g., 20% mannitol) and acetazolamide.Ifnotrelieved,thenlaserorsurgical peripheral iridectomy should be performed to bypass the pupillary block. 5. Postoperative anterior uveitis can be induced by instrumental trauma, undue handling of uveal tissue, reaction to residual cortex or chemical reaction induced by viscoelastics, pilocarpine etc. Managementincludes more aggressive use of topical steroids, cycloplegics and NSAIDs. Rarely systemic 214 Section II Diseases of Eye steroids may be required in cases with severe fibrinous reaction. 6. Toxic anterior segment syndrome (TASS) (see page 171) 7. Bacterial endophthalmitis. This is one of the most dreaded complications with an incidence of 0.2 to 0.5%. The principal sources of infection are contaminated solutions, instruments, surgeon’s hands, patient’s own flora from conjunctiva, eyelids and airborne bacteria. Symptoms and signs of bacterial endophthalmitis are generally present between 48 and 72 hours after surgery and include: ocular pain, diminshed vision, lid oedema, conjunctival chemosis and marked circumciliary congestion, corneal oedema, exudates in pupillary area, hypopyon and diminished or absent red pupillary glow. Management. It is an emergency and should be managed energetically (see page 171). D. Late postoperative complications These complications may occur after weeks, months or years of cataract surgery. 1. Cystoid macular oedema (CME). Collection of fluid in the form of cystic loculi in the Henle’s layer of macula is a frequent complication of cataract surgery. However, in most cases it is clinically insignificant, does not produce any visual problem and undergoes spontaneous regression. In few cases, a significant CME typically produces visual diminution one to three months after cataract extraction. On funduscopy it gives honeycomb appearance. On fluorescein angiography it depicts typical flower petal pattern (see Fig. 12.25A) due to leakage of dye from perifoveal capillaries. • Etiopathogenesis. In most cases it is associated with vitreous incarceration in the wound and mild iritis. Role of some prostaglandins is being widely considered in its etiopathogenesis. • Prevention. Therefore, immediate preoperative and postoperative use of antiprostaglandins (indomethacin or flurbiprofen or ketorolac) eyedrops is recommended as prophylaxis of CME. Treatment. In cases of CME with vitreous incarceration, anterior vitrectomy along with steroids and antiprostaglandins may improve visual acuity and decrease the amount of discomfort. 2. Delayed chronic postoperative endophthalmitis is caused when an organism of low virulence (propionobacterium acne or staph epidermidis) becomes trapped within the capsular bag. It has an onset ranging from 4 weeks to years (mean 9 months) postoperatively and typically follows an uneventful cataract extraction with a PCIOL in the bag. Fungal endophthalmitis may occur rarely as delayed postoperative endophthalmitis. It is characterized by puff ball vitreous exudates. It needs to be treated by pars-plana vitrectomy and antifungal drugs administered intravitreally and orally. 3. Pseudophakic bullous keratopathy (PBK) is usually a continuation of postoperative corneal oedema produced by surgical or chemical insult to a healthy or compromised corneal endothelium. PBK is becoming a common indication of penetrating keratoplasty (PK). 4. Retinal detachment (RD). Incidence of retinal detachment is higher in aphakic patients as compared to phakics. It has been noted that retinal detachment is more common after ICCE than after ECCE and IOL implantation. Other risk factors for pseudophakic retinal detachment include vitreous loss during operation, associated myopia and lattice degeneration of the retina. 5. Epithelial ingrowth. Rarely conjunctival epithelial cells may invade the anterior chamber through a defect in the incision. This abnormal epithelial membrane slowly grows and lines the back of cornea and trabecular meshwork leading to intractable glaucoma. In late stages, the epithelial membrane extends on the iris and anterior part of the vitreous. 6. Fibrous downgrowth into the anterior chamber may occur very rarely when the cataract wound apposition is not perfect. It may cause secondary glaucoma, disorganisation of anterior segment and ultimately phthisis bulbi. 7. After cataract. It is also known as ‘secondary cataract’. It is the opacity which persists or develops after extracapsular lens extraction. Causes. (i) Residual opaque lens matter may persist as after cataract when it is imprisoned between the remains of the anterior and posterior capsule, surrounded by fibrin (following iritis) or blood (following hyphaema). (ii) Proliferative type of after cataract may develop from the left out anterior epithelial cells in the capsular bag. The proliferative hyaline bands may sweep across the whole posterior capsule. Clinical types. After-cataract may present as thickened posterior capsule opacification (PCO), or dense membranous after cataract (Fig. 9.36A) or Soemmering’s ring which refers to a thick ring of after cataract formed behind the iris, enclosed between the two layers of capsule (Fig. 9.36B) or Elschnig’spearls in which the vacuolated subcapsular Chapter 9 Diseases of Lens 215 epithelial cells are clustered like soap bubbles along the posterior capsule (Fig. 9.36C). Treatmentis as follows: i. Thin membranous after cataract and thickened posterior capsule are best treated by YAG-laser capsulotomy or discission with cystitome or Zeigler’s knife. ii. Dense membranous after cataract needs surgical membranectomy. iii. Soemmering’s ring after cataract with clean central posterior capsule needs no treatment. iv. Elschnig’s pearls involving the central part of the posterior capsule can be treated by YAG-laser capsulotomy or discission with cystitome. 8. Glaucoma-in-aphakia and pseudophakia (see page 251). E. IOL-related complications In addition to the complications of cataract surgery, following IOL-related complications may be seen: 1. Complications like cystoid macular oedema, corneal endothelial damage, uveitis and secondary glaucoma are seen more frequently with IOL implantation, especially with anterior chamber and iris supported IOLs. UGH syndrome refers to concurrent occurrence of uveitis, glaucoma and hyphaema. It used to occur commonly with rigid anterior chamber IOLs, which are not used nowadays. 2. Malpositions of IOL (Fig. 9.37). These may be in the form of decentration, subluxation and dislocation. The fancy names attached to various malpositions of IOL are: • Sunset syndrome (Inferior subluxation of IOL). • Sunrise syndrome (Superior subluxation of IOL). • Lost lens syndrome refers to complete dislocation of an IOL into the vitreous cavity. • Windshieldwipersyndrome.It results when a very small IOL is placed vertically in the sulcus. In this the superior loop moves to the left and right, with movements of the head. 3. Pupillary capture of the IOL may occur following postoperative iritis or proliferation of the remains of lens fibres. 4. Toxic anterior segment syndrome (TASS). It is the uveal inflammation excited by either the ethylene gas used for sterilising IOLs (in early cases) or by the lens material (in late cases). It is characterised by violent inflammation and need to be differentiated from endophthalmitis. DISPLACEMENTS OF LENS Displacements of the lens from its normal position (in patellar fossa) results from partial or complete rupture of the lens zonules. CLINICO-ETIOLOGICAL TYPES I. Congenital displacements These may occur in the following forms: (a) Simple ectopia lentis.In this condition, displacement is bilaterally symmetrical and usually upwards. It is transmitted by autosomal dominant inheritance. (b) Ectopia lentis et pupillae. It is an autosomal recessive disorder, characterised by displacement of the lens associated with slit-shaped pupil which is displaced in the opposite direction. Other associationsmay be cataract, glaucoma, axial myopia macrocornea, abnormal iris transillumination and retinal detachment. (c) Ectopia lentis with systemic anomalies. Salient features of some common conditions, are as follows: 1. Marfan’s syndrome. It is an autosomal dominant mesodermal dysplasia. In this condition, lens is A B C Fig. 9.36 Types of after-cataract: A, dense membranous; B, Soemmering’s ring; C, Elschnig’s pearls 216 Section II Diseases of Eye Fig. 9.37 Decentered IOL displaced upwards and temporally (bilaterally symmetrical) (Fig. 9.38). • Systemicanomaliesinclude arachnodactyly (spider fingers), long extremities, hyperextensibility of joints, high arched palate and dissecting aortic aneurysm. 2. Homocystinuria. It is an autosomal recessive, inborn error of metabolism. In it the lens is usually subluxated inferior and nasally. • Systemicfeaturesare fair complexion, malar flush, mental retardation, fits and poor motor control. • Diagnosisis established by detecting homocystine in urine by sodium nitro-prusside test. 3. Weill-Marchesani syndrome. It is condition of autosomal recessive mesodermal dysplasia. • Ocular features are spherophakia, and forward subluxation of lens (Fig. 9.39) which may cause pupil block glaucoma. • Systemic features are short stature, stubby fingers and mental retardation. Fig. 9.38 Subluxated IOL in Marfan’s syndrome 4. Ehlers-Danlos syndrome. In it the ocular features are subluxation of lens and blue sclera. The systemic featuresinclude hyperextensibility of joints and loose skin with folds. 5.Hyperlysinaemia.It is an autsomal recessive inborne error of metabolism occurring due to deficiency of the enzyme lysin alphaketoglutarate reductase. It is an extremely rare condition occasionally associated with ectopia lentis. Systemic features include lax ligaments, hypotonic muscles, seizures and mental handicap. 6. Stickler syndrome. Ectopia lentis is occasionally associated in this condition (for details see page 290). 7.Sulphite oxidase deficiency.It is a very rare autosomal recessive disorder of sulphur metabolism. Ectopia lentis is a universal ocular feature. The systemic features include progressive muscular rigidity, decerebrate posture, and mental handicap. It is a fatal disease, death usually occurs before 5 years of age. II. Traumatic displacement of the lens It is usually associated with concussion injuries. Couchingis an iatrogenic posterior dislocation of lens performed as a treatment of cataract in older days. III. Consecutive or spontaneous displacement It results from intraocular diseases giving rise to me-chanical stretching, inflammatory disintegration or degeneration of the zonules. A few common condi-tions associated with consecutive displacements are: hypermature cataract, buphthalmos, high myopia, staphyloma, intraocular tumours and uveitis. TOPOGRAPHICAL TYPES Topographically, displacements of the lens may be classified as subluxation and luxationor dislocation. Fig. 9.39 Spherophakia and forward subluxation of lens in Weill-Marchesani syndrome Chapter 9 Diseases of Lens 217 I. Subluxation It is partial displacement in which lens is moved sideways (up, down, medially or laterally), but remains behind the pupil. It results from partial rupture or unequal stretching of the zonules (Figs. 9.38 and 9.40A). Clinical features are as follows: • Defectivevisionoccurs due to marked astigmatism or lenticular myopia. • Uniocular diplopia may result from partial aphakia. • Anterior chamber becomes deep and irregular. • Iridodonesis is usually present. • Edgeofthesubluxatedlens is seen as dark crescent line on distant direct ophthalmoscopy. • And as a shining (bright) golden crescent on slit-lamp examination, Phacodonesis, i.e., trimulousness of lens may be seen. • Retinoscopy reveals hypermetropia in aphakic area and myopia (index) in phakic area. • Fundus examination shows large optic disc through phakic area and small optic disc through aphakic area. Complications of subluxated lens include: • Complete dislocation, • Cataractous changes, • Uveitis, and • Secondary glaucoma. Management. Spectacles or contact lens correction for phakic or aphakic area (whichever is better) is helpful in many cases. Surgery is controversial and usually associated with high risk of retinal detachment. Lensectomy with anterior vitrectomy may be performed in desperate cases. II. Dislocation or luxation of the lens In it all the zonules are severed from the lens. A dislocated lens may be incarcerated into the pupil or present in the anterior chamber (Fig. 9.40B), the vitreous (Fig. 9.40C) (where it may be floating—lens nutans; or fixed to retina—lens fixata), sub-retinal space, subscleral space or extruded out of the globe, partially or completely. Clinical featuresof posterior dislocation.These include: deep anterior chamber, aphakia in pupillary area, and iridodonesis. Ophthalmoscopic examination reveals lens in the vitreous cavity. Clinical features of anterior dislocationare deep anterior chamber and presence of lens in the anterior chamber. Clear lens looks like an oil drop in the aqueous. Complications associated with dislocated lens are uveitis and secondary glaucoma. Management is as below: • A lens dislocated in the anterior chamber and that incarcerated in the pupil should be removed as early as possible. • Adislocatedlensfromthevitreouscavity should be removed only if it is causing uveitis or glaucoma. From the vitreous cavity lens can be removed after total vitrectomy, either with the help of an insulated vitreous cryoprobe or by aspiration facility of vitrectomy probe (only soft cataract). CONGENITAL ANOMALIES OF THE LENS 1. Colobomaoflens. It is seen as a notch in the lower quadrant of the equator (Fig. 9.41). It is usually unilateral and often hereditary. A B C Fig. 9.40 Displacements of lens: A, subluxation; B, anterior dislocation; C, posterior dislocation 218 Section II Diseases of Eye A A B Fig. 9.42 Lenticonus anterior: A, Diagrammatic; B, Slit-lamp photograph B Fig. 9.41 Coloboma of the lens: A, Diagrammatic depiction; B, Clinical photograph 2. Congenital ectopia lentis (see lens displacement page 215). 3. Lenticonus. It refers to cone-shaped elevation of the anterior pole (lenticonus anterior, Fig. 9.42) or posterior pole (lenticonus posterior, Fig. 9.43) of the lens. Lenticonus anterior may occur in Alport’s syndrome and lenticonus posterior in Lowe’s syndrome. On distant direct ophthalmoscopy, both present as an oil globule lying in the centre of the red reflex. Slit-lamp examination confirms the diagnosis. 4. Congenital cataract. (see page 182). 5. Microspherophakia. In this condition, the lens is spherical in shape (instead of normal biconvex) and small in size (Fig. 9.39). Microspherophakia may occur as an isolated familial condition or as a feature of other syndromes e.g.,Weill-Marchesani or Marfan’s syndrome. A B Fig. 9.43 Lenticonus posterior: A, Diagrammatic; B, Slit-lamp photograph 10 Glaucoma CHAPTER OUTLINE ANATOMY AND PHYSIOLOGY Applied anatomy • • Applied physiology GLAUCOMA: AN OVERVIEW • Definition and classification of glaucoma Pathogenesis of glaucomatous ocular damage • CONGENITAL/DEVELOPMENTAL GLAUCOMAS Terminology • • • Primary congenital/developmental glaucoma Developmental glaucomas with associated anomalies PRIMARY OPEN-ANGLE GLAUCOMA AND RELATED CONDITIONS ANATOMY AND PHYSIOLOGY APPLIED ANATOMY Pathophysiology of glaucoma revolves around the aqueous humour dynamics. The principal ocular structures concerned with it are ciliary body, angle of anterior chamber and the aqueous outflow system. Ciliary body It is the site of aqueous production. Applied aspects of its anatomy have been described on page 147. Angle of anterior chamber Angle of anterior chamber plays an important role in the process of aqueous drainage. It is formed by root of iris, anterior-most part of ciliary body, scleral spur, trabecular meshwork and Schwalbe’s line(prominent end of Descemet’s membrane of cornea) (Fig. 10.1). The angle width varies in different individuals and plays a vital role in the pathomechanism of different types of glaucoma. Clinically, the angle structures can be visualised by gonioscopic examination (see page 568). Gonioscopic grading of the angle width. Various systems have been suggested to grade angle width. • Primary open-angle glaucoma Ocular hypertension Normal tension glaucoma • • PRIMARY ANGLE-CLOSURE DISEASE Epidemiology • • • • • • • Etiopathogenesis Classification Clinical profile & management Primary angle-closure suspect Primary angle-closure Primary angle-closure glaucoma SECONDARY GLAUCOMAS SURGICAL PROCEDURES FOR GLAUCOMA ThemostcommonlyusedShaffer’ssystemofgrading the angle is given in Table 10.1 and is shown in Fig. 10.2. Aqueous outflow system It includes the trabecular meshwork, Schlemm’s canal, collector channels, aqueous veins and the episcleral veins (Fig. 10.3). 1. Trabecular meshwork. It is a sieve-like structure through which aqueous humour leaves the eye. It consists of three layers, which from inside out Fig. 10.1 Section of the anterior ocular structures showing region of the anterior chamber 220 Section III Diseases of Eye Table 10.1 Shaffer’s system of grading the angle width Grade Angle width 4 40° 3 30° 2 20° 1 10° S <10° 0 0° Configuration Wide open Open angle Moderately narrow Very narrow Slit angle Closed Risk of closure Closure impossible Closure impossible Closure possible High risk of closure Closure imminent Closed Structures visible on gonioscopy SL, TM, SS, CBB SL, TM, SS SL, TM SL only No angle structures seen None of the angle structures visible SL = Schwalbe’s line, TM = Trabecular meshwork, SS = Scleral spur, CBB = Ciliary body band A Fig. 10.3 The aqueous outflow system B Fig. 10.2 Diagrammatic depiction of various angle structures (SL, Schwalbe’s line; TM, trabecular meshwork; SS, scleral spur; CBB, ciliary body band: ROI root of iris) as seen in different grades of angle width (Schaffer’s grading system): A, gonioscopic view; B, configuration of the angle in cross section of the anterior chamber are uveal meshwork, corneoscleral meshwork and juxtacanalicular meshwork. i. Uveal meshwork. It is the innermost part of trabecular meshwork and extends from the iris root and ciliary body to the Schwalbe’s line. The arrangement of uveal trabecular bands create openings of about 25m to 75m. ii. Corneoscleral meshwork. It forms the larger middle portion which extends from the scleral spur to the lateral wall of the scleral sulcus. It consists of sheets of trabeculae that are perforated by elliptical openings which are smaller than those in the uveal meshwork (5m–50m). iii.Juxtacanalicular (endothelial) meshwork. It forms the outermost portion of trabecular meshwork and consists of juxtacanalicular space (filled with ground substance) and cells. The juxtacanalicular cell cytoplasmic processes attach externally to the processes arising from the innerwall endothelium of Schlemm’s canal and internally to the processes arising from the cells of corneoscleral meshwork. Thus, this narrow part of trabeculum connects the corneoscleral meshwork with Schlemm’s canal. This part of trabecular meshwork mainly offers normal resistance to the aqueous outflow. 2. Schlemm’s canal. This is an endothelial lined oval channel present circumferentially in the scleral sulcus. The endothelial cells of its inner wall are irregular, spindle-shaped and contain giant vacuoles and or aqueous valve. The outer wall of the canal is lined by smooth flat cells and contains the openings of collector channels. Chapter 10 Glaucoma 221 3. Collector channels. These, also called intrascleral aqueous vessels, are about 25–35 in number and leave the Schlemm’s canal at oblique angles to terminate into episcleral veins in a laminated fashion. These intrascleral aqueous vessels can be divided into two systems (Fig. 10.3): ■Direct system. It is formed by the larger vessels (aqueous veins) which run a short intrascleral course and terminate directly into episcleral veins. ■Indirect system. It is formed by the smaller collector channels which form an intrascleral plexus before eventually going into episcleral veins. APPLIED PHYSIOLOGY The physiological processes concerned with the dynamics of aqueous humour are its production, drainage and maintenance of intraocular pressure. Aqueous Humour and its Production Functions and composition of aqueous humour Volume. The aqueous humour is a clear watery fluid filling the anterior chamber (0.25 ml) and posterior chamber (0.06 ml) of the eyeball. Functions of aqueous humour are: • Maintenance of a proper intraocular pressure. • Metabolic and nutritional role. It plays an important metabolic role by providing substrates (nutrition) and by removing metabolites from the avascular cornea and lens. • Optical function. It maintains optical transparency. • Clearing function. Aqueous humour serves as a mechanism to clear blood, macrophages, remnants of lens matter and products of inflammation from anterior chamber. Thus, it takes the place of lymph that is absent within the eyeball. Refractive index of aqueous humour is 1.336. Composition. Constituents of normal aqueous humour are: • Water 99.9% and solids 0.1% (given below). • Proteins (colloid content). Because of blood aqueous barrier the protein content of aqueous humour (5–16 mg%) is much less than that of plasma (6–7 gm%). However, in inflammation of uvea (iridocyclitis) the blood-aqueous barrier is broken and the protein content of aqueous is increased (plasmoid aqueous). • Amino acid constituent of aqueous humour is about 5 mg/kg water. • Noncolloid constituents in millimols/kg water are glucose (6.0), urea (7), ascorbate (0.9), lactic acid (7.4), inositol (0.1), Na+ (144), K+ (4.5), Cl– (10), and HCO – (34). 3 • Oxygen is present in the aqueous humour in dissolved state. Note. Thus, composition of aqueous is similar to plasma except that it has: • High concentrations of bicarbonate, ascorbate, pyruvate and lactate; and • Low concentration of protein, urea and glucose. Aqueous humour: anterior chamber versus posterior chamber. The composition of aqeuous humour in anterior chamber differs from that of the aqueous humour in posterior chamber because of metabolic interchange. The main differences are: • HCO3 in posterior chamber aqueous is higher than – in the anterior chamber. • Cl– concentration in posterior chamber is lower than in the anterior chamber. • Ascorbate concentration of posterior aqueous is slightly higher than that of anterior chamber aqueous. Aqueous humour formation Aqueous humour is derived from plasma within the capillary network of ciliary processes. The normal aqueous production rate is 2.3 ml/min. The three mechanisms diffusion, ultrafiltration and secretion (active transport) play a part in its production at different levels. The steps involved in the process of production are summarized below: 1. Ultrafiltration. First of all, by ultrafiltration, most of the plasma substances pass out from the capillary wall and loose connective tissue. Thus, the plasma filtrate (dialysate) accumulates behind the pigmented and nonpigmented epithelium of ciliary processes. 2. Secretion. First the dialysate from the plasma is transported into the pigment epithelium. Paired Na+/ H+ and Cl–/HCO3– antiports actively transports Na+ and Cl– from the stroma into the cells. Intercellular gap junctions also play critical rule. The tight junctions between the cells of the nonpigment epithelium create part of blood aqueous barrier. Certain substances are actively transported (secreted) across this barrier into the posterior chamber. The active transport is brought about by Na+-K+ activated ATPase pump, calcium and voltage gated ion channels and carbonic anhydrase enzyme system. Substances that are actively transported include sodium, chlorides, potassium, ascorbic acid, amino acids and bicarbonates. 3. Diffusion. Active transport of these substances across the nonpigmented ciliary epithelium results in an osmotic gradient leading to the movement of other plasma constituents into the posterior 222 Section III Diseases of Eye chamber by ultrafiltration and diffusion. Sodium is primarily responsible for the movement of water into the posterior chamber. As the aqueous humour passes from the posterior chamber to Schlemm’s canal, there occurs sufficient diffusional exchange with the surrounding structures (ciliary body, iris lens, cornea and trabecular meshwork). As a result the anterior chamber aqueous resembles plasma more closely than does the posterior chamber aqueous humour. Control of aqueous formation The diurnal variation in intraocular pressure certainly indicates that some endogenous factors do influence the aqueous formation. The exact role of such factors is yet to be clearly understood. Vasopressin and adenyl-cyclase have been described to affect aqueous formation by influencing active transport of sodium. Ultrafiltration and diffusion, which primarily operate against concentration gradient, the passive mechanisms of aqueous formation, are dependent on the level of blood pressure in the ciliary capillaries, the plasma osmotic pressure and the level of intraocular pressure. Drainage of Aqueous Humour Aqueous humour flows from the posterior chamber into the anterior chamber through the pupil against slight physiologic resistance. From the anterior chamber the aqueous is drained out by two routes (Fig. 10.5): 1. Trabecular (conventional) outflow Trabecular meshwork is the main outlet for aqueous from the anterior chamber. Approximately 70–80% of the total aqueous is drained out via this route. Free flow of aqueous occurs from trabecular meshwork up to inner wall of Schlemm’s canal which appears to provide some resistance to outflow. Mechanism of aqueous transport across inner wall of Schlemm’s canal. Various theories put forward to explain the flow of aqueous across the inner wall of Schlemm’s canal can be grouped as below: I. Passive filter mechanisms. Earlier it was believed that from the juxtacanalicular space. The aqueous humour enters the Schlemm’s canal against slight resistance. Following mechanisms were postulated which are now discarded and have become a part of historical interest only: • Leaky pores in endothelial cells forming the inner wall of Schlemm’s canal were proposed. • Contractile microfilaments in the endothelial cells were suggested by some workers. • Sondermann’s channels were also suggested to be responsible for aqueous outflow the inner wall of Schlemm’s canal. • Vacuolation theory. It was one of the most accepted view till recent past. According to it, transcellular spaces exist in the endothelial cells forming inner wall of Schlemm’s canal. These open as a system of vacuoles and pores, primarily in response to pressure, and transport the aqueous from the juxtacanalicular connective tissue to Schlemm’s canal (Fig. 10.4). II. Aqueous outflow active pump mechanism. Aqueous flow through the aqueous outflow system has long been considered a passive filter mechanism against the pressure gradient. However, recently it has been reported that aqueous outflow system acts as a biomechanical pump. It has been proposed that: ■Aqueous outflow pump operates through oscillatory pressure transients caused by the ocular pulse, blinking and eye movements. • Trabecular meshwork actively moves outward and recoils back in response to the oscillatory pressure transients. Thus, trabecular meshwork flexibility is essential for the aqueous outflow pump mechanism. • Aqueous valve mechanism has been reported to operate at the level of inner wall of Schlemm’s canal (SC). These valves are oriented circumferentially in SC and their lumen is continuous with the juxtacanalicular space. These valves allow one way passage of aqueous humour from the juxtacanalicular space to inside the SC and not vice–versa. • Aqueous outflowpump system is a part of vascular circulatory loop. During cardiac diastole the IOP is slightly decreased due to less blood flow to the choroidal vasculature. As a consequence, the trabecular meshwork is retracted inward leading to a negative pressure inside the Schlemm’s canal and opening of the aqueous valves. This is followed by flow of aqueous inside the SC. • Aqueous humour flow from SC to collector’s channels and episcleral venis. During cardiac systole the choroidal vasculature explansion leads to transient rise in IOP. The aqueous pulse wave distends the trabecular meshwork (TM) forcing it outward against the SC. As a consequence of this pressure push the aqueous valves close and aqueous from the SC is pushed through the collector channels in its outer wall into the aqueous veins. Chapter 10 Glaucoma 223 A B Fig. 10.4 Vacuolation theory of aqueous transport across the inner wall of the Schlemm’s canal: 1. Nonvacuolated stage; 2. Stage of early infolding of basal surface of the endothelial cell; 3. Stage of macrovacuolar structure formation; 4. Stage of vacuolar transcellular channel formation; 5. Stage of occlusion of the basal infolding • From aqueous veins the aqueous is pushed into the episcleral veins by the same mechanism. The pressure gradient between IOP (16 mm of Hg ) and episcleral venous pressure (about 10 mm of Hg) also facilitates this unidirectional pulsatile flow of aqueous humour. 2. Uveoscleral (unconventional) outflow It is responsible for about 20 to 30% of the total aqueous outflow. The aqueous enters the ciliary body through the iris root, ciliary body face and uveal trabecular meshwork. Aqueous passes across the ciliary body between the bundles of ciliary muscles into the suprachoroidal space and is drained by the venous circulation of the ciliary body, choroid and sclera. The drainage of aqueous humour is summarized in the flowchart (Fig. 10.5). Maintenance of Intraocular Pressure The intraocular pressure (IOP) refers to the pressure exerted by intraocular fluids on the coats of the eyeball. The normal IOP varies between 10 and 21 mm of Hg (mean 16 + 2.5 mm of Hg). The normal level of IOP is essentially maintained by a dynamic equilibrium between the formation and outflow of the aqueous humour. Various factors influencing intraocular pressure can be grouped as under: A. Local factors 1. Rate of aqueous formation influences IOP levels. The aqueous formation in turn depends upon Fig. 10.5 Flow chart depicting drainage of aqueous humour many factors such as permeability of ciliary capillaries and osmotic pressure of the blood. 2. Resistance to aqueous outflow (drainage). From clinical point of view, this is the most important factor. Most of the resistance to aqueous outflow is at the level of trabecular meshwork. 3. Increased episcleral venous pressure may result in rise of IOP. The Valsalva manoeuvre causes 224 Section III Diseases of Eye temporary increase in episcleral venous pressure and rise in IOP. 4. Dilatation of pupil in patients with narrow anterior chamber angle may cause rise of IOP owing to a relative obstruction of the aqeuous drainage by the iris. 5. Refractive errors. Myopic individuals have higher IOP as compared to emmetropes and hypermetropes. Infact, IOP correlates with axial length. B. General factors 1. Heredity. It influences IOP, possibly by multi-factorial modes. 2. Age. The mean IOP increases after the age of 40 years, possibly due to reduced facility of aqueous outflow. 3. Sex. IOP is equal between the sexes in ages 20–40 years. In older age groups increase in mean IOP with age is greater in females. 4. Diurnal variation of IOP. Usually, there is a tendency of higher IOP in the morning and lower in the late evening (Fig. 10.9). This has been related to diurnal variation in the levels of plasma cortisol. Normal eyes have a smaller fluctuation (<5 mm of Hg) than glaucomatous eyes (>8 mm of Hg). 5. Postural variations. IOPincreases when changing from the sitting to the supine position. 6. Seasonal variations. IOP is higher in winter months. 7. Blood pressure. As such it does not have long-term effect on IOP. However, prevalence of glaucoma is marginally more in hypertensives than the normotensives. 8. Osmotic pressure of blood. An increase in plasma osmolarity (as occurs after intravenous mannitol, oral glycerol or in patients with uraemia) is associated with a fall in IOP, while a reduction in plasma osmolarity (as occurs with water drinking provocative tests) is associated with a rise in IOP. 9. General anaesthetics and many other drugs also influence IOP, e.g., alcohol lowers IOP, tobacco smoking, caffeine and steroids may cause rise in IOP. In addition there are many antiglaucoma drugs which lower IOP. 10.Exercise. Strenous exercise lowersIOP transiently. GLAUCOMA: AN OVERVIEW DEFINITION AND CLASSIFICATION OF GLAUCOMA Definition Glaucoma is not a single disease process but a group of disorders characterized by a progressive optic neuropathy resulting in a characterstic appearance of the optic disc and a specific pattern of irreversible visual field defects that are associated frequently but not invariably with raised intraocular pressure (IOP). Thus, IOP is the most common risk factor but not the only risk factor for development of glaucoma. Consequently the term ‘ocular hypertension’ is used for cases having constantly raised IOP without any associated glaucomatous damage. Conversely, the term normal or low tension glaucoma (NTG/LTG) is suggested for the typical cupping of the disc and/ or visual field defects associated with a normal or low IOP. Classification Clinico-etiologically glaucoma may be classified as follows: A. Congenital/developmental glaucomas 1. Primary congenital glaucoma (without associated anomalies). 2. Developmental glaucoma (with associated anomalies). B. Primary adult glaucomas 1. Primary open-angle glaucomas (POAG) 2. Primary angle-closure glaucoma (PACG) 3. Primary mixed mechanism glaucoma C. Secondary glaucomas EPIDEMIOLOGY Global prevalence of glaucoma • 2% of those over the age of 40 years, and • 10% of those over 80 years of age. POAG Versus PACG in different ethnic groups Ethnic group POAG : PACG ■Indian 1 : 1 ■Urban Chinese 1 : 2 ■Mongolian 1 : 3 ■European, African 5 : 1 and Hispanic Glaucoma blindness • Global : 8.0% • India : 12.8% PATHOGENESIS OF GLAUCOMATOUS OCULAR DAMAGE As mentioned in definition, all glaucomas (classified above and described later) are characterized by a progressive optic neuropathy. It has now been recognized that progressive optic neuropathy results from the death of retinal ganglion cells (RGCs) in a typical pattern which results in characteristic optic disc appearance and specific visual field defects. Chapter 10 Glaucoma 225 Pathogenesis of Retinal Ganglion Cell Death Retinal ganglion cell (RGC) death is initiated when some pathologic event blocks the transport of growth factors (neurotrophins) from the brain to the RGCs. The blockage of these neurotrophins initiate a damaging cascade, and the cell is unable to maintain its normal function. The RGCs losing their ability to maintain normal function undergo apoptosis and also trigger apoptosis of adjacent cells. Apoptosis is a genetically controlled cell suicide programme whereby irreversibly damaged cells die, and are subsequently engulfed by neighbouring cells, without eliciting any inflammatory response. Retinal ganglion cell death is, of course, associated with loss of retinal nerve fibres. As the loss of nerve fibres extends beyond the normal physiological overlap of functional zones, the characteristic optic disc changes and specific visual field defects become apparent over the time. Etiological factors Factors involved in the etiology of retinal ganglion cell death and thus in the etiology of glaucomatous optic neuropathy can be grouped as below: A. Primary insults 1. Raised intraocular pressure (Mechanical theory). Raised intraocular pressure causes mechanical stretch on the lamina cribrosa leading to axonal deformation and ischaemia by altering capillary blood flow. As a result of this, neurotrophins (growth factors) are not able to reach the retinal ganglion cell bodies in sufficient amount needed for their survival. 2. Pressure independent factors (Vascular insuffciency theory). Factors affecting vascular perfusion of optic nerve head in the absence of raised IOP have been implicated in the glaucomatous optic neuropathy in patients with normal tension glaucoma (NTG). However, these may be the additional factors in cases of raised IOP as well. These factors include: i. Failure of autoregulatory mechanism of blood flow. The retina and optic nerve share a peculiar mechanism of autoregulation of blood flow with rest of the central nervous system. Once the autoregulatory mechanisms are compromised, blood flow may not be adequate beyond some critical range of IOP (which may be raised or in normal range). ii. Vasospasm is another mechanism affecting vascular perfusion of optic nerve head. This hypothesis gets credence from the convincing association between NTG and vasospastic disorders (migranous headache and Raynaud’s phenomenon). iii. Systemic hypotension, particularly nocturnal dips in patients with night time administration of antihypertensive drugs, has been implicated for low vascular perfusion of optic nerve head resulting in NTG and progression of damage in POAG. iv. Other factors such as acute blood loss and abnormal coagulability profile have also been associated with NTG. B. Secondary insults (Excitotoxicity theory) Neuronal degeneration is believed to be driven by toxic factors such as glutamate (excitatory toxin), oxygen-free radicals, or nitric oxide which are released when RGCs undergo death due to primary insults. In this way, the secondary insult leads to continued damage-mediated apoptosis, even after the primary insult has been controlled. CONGENITAL/DEVELOPMENTAL GLAUCOMAS TERMINOLOGY The congenital glaucomas are a group of diverse disorders in which abnormal high intraocular pressure results due to developmental abnormalities of the angle of anterior chamber obstructing the drainage of aqueous humour. Sometimes, glaucoma may not occur until several years after birth; therefore, the term developmental glaucoma is preferred to describe such disorders. Types 1.Primary developmental/congenital glaucoma. 2.Developmental glaucoma with associated congenital ocular anomalies. 3.Developmental glaucoma with associated systemic anomalies. PRIMARY CONGENITAL/DEVELOPMENTAL GLAUCOMA Primary congenital glaucoma (PCG) refers to abnor-mally high IOP which results due to developmental anomaly of the angle of the anterior chamber, not associated with any other ocular or systemic anomaly. Depending upon the age of onset the developmental glaucomas are termed as follows: 1. Newborn glaucoma, also called as true congenital glaucoma, is labelled when IOP is raised during intrauterine life and child is born with ocular enlargement. It accounts for about 40% of cases. 2. Infantile glaucoma is labelled when the disease manifests prior to the child’s third birthday. It accounts for about 55% of cases. 3. Juvenile glaucoma is labelled in the rest 5% of cases who develop pressure rise after 3 years but before adulthood. Also known as Juvenile primary open 226 Section III Diseases of Eye angle glaucoma(POAG) usually occurs between 10 to 35 years of age. About 35% of patients with juvenile POAG are myopes. The disease has a strong autosomal dominant inheritance . Some of the families suffering from juvenile POAG have a genetic anomaly on the long arm of chromosome 21. Buphthalmos. When the disease manifests prior to age of 3 years, the eyeball enlarges and so the term ‘buphthalmos’ (bull-like eyes) is used. As it results due to retention of aqueous humour (watery solution), the term ‘hydrophthalmos,’ has also been suggested. Prevalence and genetic pattern • Sporadic occurrence is seen in most cases (90%). • Autosomal recessive inheritance with incomplete penetrance is seen in about 10% cases. • Loci linked with PCG are 2p21(GLC3A), 1p36 (GLC3B) and 14q24 (GLC3C). • Sex linkage is not common in inheritance although over 65% of the patients are boys. • Bilateral occurrence is seen in 70% cases, though the involvement may be asymmetric. • Prevalence of the disease is only 1 child in 10,000 births. Pathogenesis Maldevelopment, from neural crest derived cells, of trabeculum including the iridotrabecular junction (trabeculodysgenesis) is responsible for impaired aqueous outflow resulting in raised IOP. In primary congenital glaucoma, the trabeculodysgenesis is not associated with any other major ocular anomalies. Clinically, trabeculodysgenesis is characterized by absence of the angle recess with iris having a flat or concave direct insertion into the surface of trabeculum as follows: ■Flat iris insertion is more common than the concave iris insertion. In it the iris inserts flatly and abruptly into the thickened trabeculum either at or anterior to scleral spur (more often) or posterior to scleral spur. It is often possible to visualize a portion of ciliary body and scleral spur. ■Concave iris insertion is less common. In it the superficial iris tissue sweeps over the iridotrabecular junction and the trabeculum and, thus, obscures the scleral spur and ciliary body. Clinical features 1. Lacrimation, photophobia and blepharospasm often occur together and form the classic triad of symptoms of congenital glaucoma. Often there is history of rubbing of the eyes. These are thought to be caused by irritation of corneal nerves, which occurs as a result of the elevated IOP. Photophobia is usually the initial sign, but is not enough by itself to arouse suspicion in most cases. 2. Corneal signs. Corneal signs include its oedema, enlargement and Descemet’s breaks. i. Corneal oedema. It is frequently the first sign which arouses suspicion. At first it is epithelial, but later there is stromal involvement and permanent opacities may occur. ii. Corneal enlargement. It occurs alongwith enlargement of globe-buphthalmos (Fig. 10.6), especially when the onset is before the age of 3 years. Normal infant cornea measures 10.5 mm. A diameter of more than 13 mm confirms enlargement. Prognosis is usually poor in infants with corneal diameter of more than 16 mm. iii. Tears and breaks in Descemet’s membrane (Haab’s striae). These occur because Descemet’s membrane is less elastic than the corneal stroma. Tears are usually peripheral, concentric with the limbus and appear as lines with double contour. 3. Sclera becomes thin and appears blue due to underlying uveal tissue. 4. Anterior chamber becomes deep. 5. Iris may show iridodonesis and atrophic patches in late stage. 6. Lens becomes flat due to stretching of zonules and may even subluxate backward. 7. Optic disc may show variable cupping and atrophy especially after third year. 8. IOP is raised which is neither marked nor acute. 9. Axial myopia may occur because of increase in axial length which may give rise to anisometropic amblyopia. Examination (Evaluation) A complete examination under general anaesthesia (EUA) should be performed on each child suspected of having congenital glaucoma. The examination should include following: 1. Measurement of IOP with Schiotz or preferably hand held Perkin’s applanation tonometer since scleral rigidity is very low in children. IOP measurement under GA is unpredictably altered. Fig. 10.6 Corneal enlargement in a child with congenital glaucoma Chapter 10 Glaucoma 227 2. Measurement of corneal diameter by callipers. 3. Slit-lamp examination should be carried out with portable slit-lamp. 4. Ophthalmoscopy to evaluate optic disc. 5. Gonioscopic examination of angle of anterior chamber reveals trabeculodysgenesis with either flat or concave iris insertion as described in pathogenesis. Differential diagnosis It is to be considered for different presenting signs as follows: 1. Cloudy cornea. In unilateral cases, the commonest cause is trauma with rupture of Descemet’s membrane (forceps injury). In bilateral cases, causes may be trauma, mucopolysaccharidosis, interstitial keratitis and corneal endothelial dystrophy. 2. Large cornea due to buphthalmos should be differentiated from megalocornea, sclerocornea and high myopia. 3. Lacrimation in an infant is usually considered to be due to congenital nasolacrimal duct blockage and thus early diagnosis of congenital glaucoma may be missed. Other causes of watering in small child include corneal abrasion, Meesman’s corneal dystrophy and Reis-Buckler dystrophy. 4. Photophobia may be due to keratitis or uveitis. 5. Raised IOP in infants may also be associated with retinoblastoma, retinopathy of prematurity, persistent primary hyperplastic vitreous, traumatic glaucoma and secondary congenital glaucoma seen in rubella, aniridia and Sturge-Weber syndrome. 6. Optic disc changes need to be differentiated from congenital anomalies of the disc such as pit, coloboma, hypoplasia, tilted disc and large physiological cup. Treatment Medical treatment Medications are not very effective and so treatment of congenital glaucoma is primarily surgical. However, IOP must be lowered by medical treatment with hyperosmotic agents, acetazolamide and beta-blockers till surgery is taken up. Miotics are not used in such cases because they paradoxically increase IOP. Alpha-2 agonist (brimonidine) causes CNS depression in children and is contraindicated. Surgical procedures for congenital glaucoma I. Incisional angle surgery, which can be performed by the internal approach (goniotomy) or by external approach (trabeculectomy). 1.Goniotomy(Fig. 10.7). In this procedure, a Barkan’s goniotomy knife is passed through the limbus on the temporal side. Under gonioscopic control the knife A B Fig. 10.7 Technique of goniotomy: A, showing position of goniotomy knife in the angle under direct visualization; B, showing procedure of sweeping the knife in the angle is passed across the anterior chamber to the nasal part of the angle. An incision is made in the angle approximately midway between root of the iris and Schwalbe’s ring through approximately 75°. The knife is then withdrawn. Although the procedure may have to be repeated, the eventual success rate is about 85%. 2.Trabeculotomy. This is useful when corneal clouding prevents visualization of the angle or in cases where goniotomy has failed. In this, canal of Schlemm is exposed at about 12 O’clock position by a vertical scleral incision after making a conjunctival flap and partial thickness scleral flap. The lower prong of Harm’s trabeculotome is passed along the Schlemm’s canal on one side and the upper prong is used as a guide (Fig. 10.8). Then the trabeculotome is rotated so as to break the inner wall over one quarter of the canal. This is then repeated on the other side. The main difficulty in this operation is localization of the Schlemm’s canal. II. Filteration surgery is required in many cases: 1. Trabeculectomy with antimetabolites gives good results. 2. Combined trabeculotomy and trabeculectomy with antimetabolites has been accepted as the standard procedure. III. Glaucoma drainage devices (GDD) are required in incalcitrant cases. 228 Section III Diseases of Eye Fig. 10.8 Technique of trabeculotomy DEVELOPMENTAL GLAUCOMAS WITH ASSOCIATED OCULAR ANOMALIES A wide variety of systemic and/or ocular anomalies have an associated raised IOP, usually due to developmental defects of the anterior chamber angle. Some of the associations are as follows: I. Glaucoma associated with iridodysgenosis 1. Glaucoma associated with aniridia (50%) 2. Glaucoma associated with familial iris hypoplasia 3. Glaucoma associated with congenital ectropion uvea 4. Glaucoma associated with congenital microcornea 5. Glaucoma associated with congenital nanop- hthalmos II. Glaucoma associated with iridocorneal dysgenesis These include: 1.Posterior embryotoxon characterized by a prominent Schwalbe’s ring. 2. Axenfeld-Rieger syndrome refers to the spectrum of following anomalies: • Axenfeld anomaly is characterized by posterior embryotoxon with attachment of strands of peripheral iris tissue. • Rieger anomaly is characterized by posterior embryotoxon, iris stomal hypoplasia, ectropion uveal corectopia, and full thickness iris defect. • Rieger syndrome refers to Rieger anomaly associated with dental anomalies (hypodentia or microdential), facial anomalies (maxillary hypoplasia, broad nasal bridge, telecanthus and hypertelorism) and other anomalies (hypospadias, redundant paraumblical skin, and renal anomalies). 3. Peter’s anomalyis characterized by central corneal opacity with or without irido-corneal or lenticulo-corneal adhesions. It may have other ocular and some systemic associations as well. 4. Combined Reiger’s syndrome and Peters anomaly is characterized by features of the both described above. DEVELOPMENTAL GLAUCOMA WITH ASSOCIATED SYSTEMIC ANOMALIES 1. Glaucomaassociated with chromosal disorders such as trisomy 13–15 (trisomy D syndrome), trisomy 18 (Edward’s syndrome), trisomy 21 (Down’s syndrome) and Turner’s syndrome. 2. Glaucoma associated with ectopia lentis syndromes, which include Marfan’s syndrome, Weil-Marchesani syndrome and homocystinuria. 3. Glaucoma associated with phakomatosis is seen in Sturge-Weber syndrome (50% cases) and Von Recklinghausen’s neurofibromatosis (25% cases). 4.Glaucoma associated with metabolic syndromes such as:Lowe’s syndrome (oculo-cerebrorenal syndrome), Hurler’s syndrome (mucopolysaccharidosis) and Zellweger syndrome (hepato-cerebral renal syndrome). PRIMARY OPEN-ANGLE GLAUCOMA AND RELATED CONDITIONS PRIMARY OPEN-ANGLE GLAUCOMA As the name implies, it is a type of primary glaucoma, where there is no obvious systemic or ocular cause of rise in the intraocular pressure. Primary open-angle glaucoma (POAG), also known as chronic simple glaucoma of adult onset, is typically characterised by: • Slowly progressive raised intraocular pressure (>21 mm Hg recorded on at least few occasions) associated with, • Open normal appearing anterior chamber angle, • Characteristic optic disc cupping, and • Specific visual field defects. ETIOPATHOGENESIS Etiopathogenesis of POAG is not known exactly. Some of the known facts are as follows: Chapter 10 Glaucoma 229 A. Predisposing and risk factors. These include the following: 1. Intraocular pressure (IOP), is the most important risk factor for development of POAG. 2. Family history (Heredity). The approximate risk of getting disease is 10% in the siblings, and 4% in the offspring of patients with POAG. POAG has a polygenic inheritance, approximately two dozen loci have been identified for POAG out of which only following three genes have been coloned: • Myocilin C (MYOC), • Optineurin (OPTN), and • WD repeat domain 36 (WDR 36) 3. Age. The risk increases with increasing age. The POAG is more commonly seen in elders between 5th and 7th decades. 4. Race. POAG is significantly more common, develops earlier and is more severe in black people than in white. 5. Myopes are more predisposed than the normals. 6. Central corneal thickness (CCT). A thinner CCT, apart from causing underestimation of IOP by applanation tonometer, is being considered as an independent risk factor for POAG. 7. Diabetics have a higher prevalence of POAG than nondiabetics. 8. Cigarette smoking is also thought to increase its risk. 9. High blood pressure is not the cause of rise in IOP, however, the prevalence of POAG is more in hypertensives than the normotensives. Most meaningful blood pressure variable related to glaucoma is diastolic perfusion pressure (diastolic blood pressure–IOP). A diastolic perfusion pressure of <55 mm Hg is an important risk factor for glaucoma. 10. Thyrotoxicosis is also not the cause of rise in IOP, but the prevalence of POAG is more in patients suffering from Graves’ ophthalmic disease than the normals. 11. Corticosteroid responsiveness. Patients with POAG and their offspring and sibilings are more likely to respond to 6 weeks topical steroid therapy with a significant rise of IOP. B. Pathogenesis of rise in IOP. It is certain that rise in IOP occurs due to decrease in the aqueous outflow facility. Recently it has been proposed that reduced aqueous outflow facility occurs due to failure of aqueous outflow pump mechanism owing to trabecular meshwork stiffening and apposition of Schlemm’s canal wall. Such changes are caused by: • Thickening and sclerosis of trabecular meshwork with faulty collagen tissue. • Narrowing of intertrabecular spaces. • Deposition of amorphous material in the juxtacanalicular space. • Collapse of Schlemm’s canal and absence of giant vacuoles in the cells lining it. The exact cause of these changes is uncertain. Detection of increased gammaglobulin and plasma cells in trabecular meshwork on immunohisto-chemistry and positive antinuclear antibody reaction in some cases support an immunogenic mechanism in POAG. C. Pathogenesis of optic neuropathy. (see page 224) EPIDEMIOLOGY OF POAG POAG affects about 1 in 100 of the general population (of either sex) above the age of 40 years. It forms about one-third cases of all glaucomas. Prevalence of POAG varies in different populations is as below: Ethnic group POAG : PACG • Europeans, Africans and 5 : 1 Hispanics • Mongolian 1 : 3 • Urban Chinese 1 : 2 • Indian 1 : 1 CLINICAL FEATURES Symptoms 1. Asymptomatic. The disease is insidious and usually asymptomatic, until it has caused a significant loss of visual field. Therefore, periodic eye examination is required after middle age. 2. Headache and eye ache of mild intensity may be experienced in the course of the disease. 3. Scotoma (defect in the visual field) may be noticed occasionally by some observant patients. 4. Difficulty in reading and close work, often persistently increasing, is experienced by most patients. This occurs due to increasing accommodative failure as a result of constant pressure on the ciliary muscle and its nerve supply. Therefore, patients usually complain of, frequent changes in presbyopic glasses. 5. Delayed dark adaptation may develop, a disability which becomes increasingly disturbing in the late stages. 6. Significant loss of vision and blindness is the end result of untreated cases of POAG. Signs I. Anterior segment signs Ocular examination including slit-lamp biomicroscopy may reveal normal anterior segment. In late stages, pupil reflex becomes sluggish and 230 Section III Diseases of Eye corneamayshowslight haze. A low(<555mm)central corneal thickness (CCT) is a significant risk factor for POAG. II. lntraocular-pressure changes In the initial stages, the IOP may not be raised permanently, but there is an exaggeration of the normal diurnal variation. Therefore, repeated observations of IOP (every 3–4 hour), for 24 hours is required during this stage (Diurnal variation test). In most patients, IOP falls during the evening, contrary to what happens in angle-closure glaucoma. Different patterns of diurnal variation of IOP shown in Fig. 10.9 are: • Morning rise in IOP–20% of cases • Afternoon rise in IOP–25% of cases • Biphasic rise in IOP–55% of cases A variation in IOP of over 5 mm Hg (Schiotz) is suspicious and over 8 mm of Hg is diagnostic of glaucoma. In later stages, IOP is permanently raised above 21 mm of Hg and ranges between 30 and 45 mm of Hg. III. Optic disc changes Optic disc changes, usually observed on routine fundus examination, provide an important clue for suspecting POAG. These are typically progressive, asymmetric and present a variety of characteristic clinical patterns. It is essential, therefore, to record the appearance of the nerve head in such a way that will accurately reveal subtle glaucomatous changes over the course of follow-up evaluation. Examination techniques. Careful fundus examination should be performed to detect optic disc changes. Best technique is to have a stereoscopic view of the optic disc with contact or noncontact lenses on slit-lamp biomicroscopic examination. Non-contact lenses (+ 78D or + 90D) are more convenient and are thus widely used. Recording and documentation techniquesinclude serial hand drawings, photography and photogrammetry. Confocal scanning laser topography (CSLT), i.e., Heidelberg retinal tomograph (HRT) is an accurate and sensitive method for this purpose. Other advanced imaging techniques include optical coherence tomography (OCT) and scanning laser polarimetry, i.e., nerve fibre analyser (NFA). Glaucomatous changes in the optic disc can be described as early changes, advanced changes and glaucomatous optic atrophy. Figs. 10.10A and B show normal disc configuration. (a) Early glaucomatous changes (Figs. 10.10C and D) should be suspected to exist if fundus examination reveals one or more of the following signs: Fig. 10.9 Patterns of diurnal variations of IOP: A, normal slight morning rise; B, morning rise seen in 20% cases of POAG; C, afternoon rise seen in 25% cases of POAG; D, biphasic variation seen in 55% cases of POAG 1. Vertically oval cup due to selective loss of neural rim tissue in the inferior and superior poles. 2. Asymmetry of the cups. A difference of more than 0.2 between two eyes is significant. 3. Large cup, i.e., 0.6 or more (normal cup size is 0.3 to 0.4) may occur due to concentric expansion. 4. Splinter haemorrhages present on or near the optic disc margin. 5. Pallor areas on the disc. Chapter 10 Glaucoma 231 C A B D Fig. 10.10 Normal optic disc (A, diagrammatic depiction; B, fundus photograph) and optic disc showing early glaucomatous changes (C, diagrammatic depiction; D, fundus photograph) 6. Atrophy of retinal nerve fibre layer which may be seen with red free light. (b) Advanced glaucomatous changes in the optic disc include: 1. Marked cupping (cup size 0.7 to 0.9), excavation may even reach the disc margin, the sides are steep and not shelving (c.f. deep physiological cup) (Figs. 10.11A and B) which are well-delineated on OCT examination (Fig. 10.11C). 2. Thinning of neuroretinal rim which occurs in advanced cases is seen as a crescentric shadow adjacent to the disc margin. Normally, the thickest to thinnest parts of the neuroretinal rim of the optic disc are inferior, superior, nasal and temporal (ISNT rule). Any variation from this helps to detect glaucoma. Notching of the rim specially up to disc margin is pathognomic. 3. Nasal shifting of retinal vessels which have the appearance of being broken off at the margin is an important sign (Bayonetting sign). When the edges overhang, the course of the vessels as they climb the sides of the cup is hidden. 4. Pulsations of the retinal arterioles may be seen at the disc margin (a pathognomic sign of glaucoma), when IOP is very high. 5. Lamellar dot sign the pores in the lamina cribrosa are slit-shaped and are visible up to the margin of the disc. (c) Glaucomatous optic atrophy. As the damage progresses, all the neural tissue of the disc is 232 Section III Diseases of Eye destroyed and the optic nerve head appears white and deeply excavated (Figs. 10.11C and D). Pathophysiology of disc changes. Both mechanical and vascular factors play a role in the cupping of the disc. Mechanical effect of raised IOP forces the lamina cribrosa backwards and squeezes the nerve fibres within its meshes to disturb axoplasmic flow. Vascular factors contribute in ischaemic atrophy of the nerve fibres without corresponding increase of supporting glial tissue. As a result, large caverns or lacunae are formed (cavernous optic atrophy). IV. Visual field defects Visual field defects appear only after about 40% of axons have been damaged and subsequently the field defects usually run parallel to the changes at the optic nerve head and continue to progress if IOP is not controlled. These can be described as early and late field defects. Anatomical basis of field defects. For better under-standing of the actual field defects, it is mandatory to have a knowledge of their anatomical basis. A D B C E Fig. 10.11 Optic disc showing advanced glaucomatous changes: A, diagramatic depiction; B, fundus photograph; C, OCT picture; D and E, diagrammatic depiction and fundus photograph of glaucomotous optic atrophy Chapter 10 Glaucoma 233 A.Distribution of retinal nerve fibres (Fig. 10.12). 1.Fibres from nasal half of the retina come directly to the optic disc as superior and inferior radiating fibres (SRF and IRF). 2.Those from the macular area come horizontally as papillomacular bundle (PMB). 3.Fibres from the temporal retina arch above and below the macula and papillomacular bundle as superior and inferior arcuate fibres with a horizontal raphe in between (SAF and IAF). B. Arrangement of nerve fibres within optic nerve head (Fig. 10.13): Those from the peripheral part of the retina lie deep in the retina but occupy the most peripheral (superficial) part of the optic disc. While fibres originating closer to the nerve head lie superficially in the retina and occupy a more central (deep) portion of the disc. The arcuate nerve fibres occupy the superior and inferior temporal portions of optic nerve head and are most sensitive to glaucomatous damage; accounting for the early loss in the corresponding regions of the visual field. Macular fibres are most resistant to the glaucomatous damage and explain the retention of the central vision till end. Fig. 10.12 Distribution of retinal nerve fibres Fig. 10.13 Arrangement of nerve fibres within optic nerve head Nomenclature of glaucomatous field defects. Visual field defects in glaucoma are initially observed in Bjerrum’s area (10–25 degree from fixation) and correlate with optic disc changes. The natural history of the progressive glaucomatous field loss, more or less, takes the following sequence: 1. Isopter contraction. It refers to mild generalised constriction of central as well as peripheral field. It is the earliest visual field defect occurring in glaucoma. However, it is of limited diagnostic value, as it may also occur in many other conditions. 2. Baring of blind spot. It is also considered to be an early glaucomatous change, but is very nonspecific and thus of limited diagnostic value. Baring of the blind spot means exclusion of the blind spot from the central field due to inward curve of the outer boundary of 30° central field (Fig. 10.14A). 3. Small wing-shaped paracentral scotoma (Fig. 10.14B). It is the earliest clinically significant field defect. It may appear either below or above the blind spot in Bjerrum’s area (an arcuate area extending above and below the blind spot between 10° and 20° of fixation point). 4. Seidel’s scotoma. With the passage of time paracentral scotoma joins the blind spot to form a sickle-shaped scotoma known as Seidel’s scotoma (Fig. 10.14C). 5. Arcuate or Bjerrum’s scotoma. It is formed at a later stage by the extension of Seidel’s scotoma in an area either above or below the fixation point to reach the horizontal line (Fig. 10.14D). Damage to the adjacent fibres causes a peripheral breakthrough. 6. Ring or double arcuate scotoma. It develops when the two arcuate scotomas join together (Fig. 10.14E). 7. Roenne’s central nasal step. It is created when the two arcuate scotomas run in different arcs and meet to form a sharp right-angled defect at the horizontal meridian (Fig. 10.14E). 8.Peripheral field defects.These appear sometimes at an early stage and sometimes only late in the disease. The peripheral nasal step of Roenne’s results from unequal contraction of the peripheral isopter. 9. Advanced glaucomatous field defects. The visual field loss gradually spreads centrally as well as peripherally, and eventually only a small island of central vision (tubular vision) and an accompanying temporal island are left. With the continued damage, these islands of vision also progressively diminish in size until the tiny central island is totally extinguished. The temporal island of the vision is more resistant and is lost in the end leaving the patient with no light perception. Diagnosis of glaucoma field defects on HFA single field printout. Glaucomatous field defects should always 234 Section III Diseases of Eye A B C D E Fig. 10.14 Field defects in POAG: A, baring of blind spot; B, superior paracentral scotoma; C, Seidel’s scotoma; D, Bjerrum’s scotoma; E, double arcuate scotoma and Roenne’s central nasal step be interpreted in conjunction with clinical features (IOP and optic disc changes). Further, before final interpretation, the fields must be tested twice, as there is often a significant improvement in the field when plotted second time (because patients become more familiar with the machine and test process). Criteria to grade glaucomatous, field defects. The criteria to label early, moderate and severe glaucomatous field defect from the HFA central 30-2 test, single printout is depicted in Table 10.2. Assessing visual field progression in glaucoma. Progression in visual defects can be judged by any of the following methods: • Comparing individual single field printouts obtained over a period of time. • Overview printout, in which up to 16 previously tested visual fields can be shown in a single printout without any stastical interpretation. • Progression analysis software (G PA in HFA machines and Peritrend in Octopus perimeter) is now available for stastical analysis of progression in the visual field defects. • Visual field index (VFI), is a new measure which uses regression to offer a trend-based analysis of the speed of visual field loss. In it a scale of 0 to 100, i.e., complete loss of the field to normal full field is generate to grade the field loss. Note. For proper understanding of Table 10.2, evaluation of the Humphrey single field printout described on page 515 should be revised. Ocular associations POAG may sometimes be associated with high myopia, Fuchs’ endothelial dystrophy, retinitis pigmentosa, central retinal vein occlusion and primary retinal detachment. INVESTIGATIONS 1. Tonometry. Applanation tonometry should be preferred over Schiotz tonometry (see page 509). 2. Central corneal thickness (CCT) measurement is essential in the workup for glaucoma since a thinner cornea underestimates and a thicker cornea overestimates the IOP on applanation tonometry. A low CCT (<545 microns) is an independent risk factor for conversion of ocular hypertension to POAG. It has been suggested that a correction factor should be applied to the IOP readings in patients with CCT less than 545 microns and more than 600 microns. 3. Diurnal variation test is especially useful in detection of early cases (see page 230). Chapter 10 Glaucoma 235 Table 10.2 Criteria to diagnose early, moderate and severe glaucomatous field defects from HFA: 30-2-test. Sr. Parameter Criteria for glaucomatous field defects no. 1. Mean deviation (MD) 2. Corrected pattern standard deviation (CPSD) 3. Pattern deviation plot Points depressed below the p < 5% Points depressed below the p < 1% 4. Glaucoma Hemifield Test (GHT) 5. Sensitivity in central 5 degree (Raw data or Numeric value in dB) Early defects <–6 dB Depressed to p < 5% <18 (25%) <10 Outside normal limits No point <15 dB Moderate defects – 6 dB – 12 dB Depressed to p < 5% <37 (50%) <20 Outside normal limits One hemifield may have point with sensitivity <15 dB No point has 0 dB Severe defects > – 12 dB Depressed to the p < 5% >37 (>50%) >20 Outside normal limits Both hemifield have points with sensitivity <15 dB Any point has 0 dB 4. Gonioscopy.It reveals a wide open angle of anterior chamber. Its primary importance in POAG is to rule out other forms of glaucoma (For details, see pages 219 and 568). 5. Documentation of optic disc changes is of utmost importance (see page 230). 6. Slit-lamp examination of anterior segment to rule out causes of secondary open-angle glaucoma. 7. Perimetry to detect the visual field defects. 8. Nerve fibre layer analyzer (NFLA) is a recently introduced device which helps in detecting the glaucomatous damage to the retinal nerve fibres before the appearance of actual visual field changes and/or optic disc changes. 9. Provocative tests are required in border-line cases. The test commonly performed is water drinking test. Other provocative tests not frequently performed include combined water drinking and tonography, bulbar pressure test, prescoline test and caffeine test. Water drinking test. It is based on the theory that glaucomatous eyes have a greater response to water drinking. In it after an 8 hours fast, baseline IOP is noted and the patient is asked to drink one litre of water, following which IOP is noted every 15 minutes for 1 hour. The maximum rise in IOP occurs in 15–30 minutes and returns to baseline level after 60 minutes in both normal and the glaucomatous eyes. A rise of 8 mm of Hg or more is said to be diagnostic of POAG. DIAGNOSIS Depending upon the level of intraocular pressure (IOP), glaucomatous cupping of the optic disc and the visual field changes (Fig. 10.15) the patients are assigned to one of the following diagnostic entities: 1. Primary open-angle glaucoma (POAG). Characteristically POAG is labelled when raised IOP (>21 mm of Hg) is associated with definite glaucomatous optic disc cupping and visual field changes. However, patients with raised IOP and either typical field defects or disc changes are also labelled as having POAG. 2. Ocular hypertension. This term is used when a patient has an IOP constantly more than 21 mm of Fig. 10.15 Triad of abnormalities in disc, field and intra-ocular pressure (IOP) for the diagnosis of glaucoma 236 Section III Diseases of Eye Hg but no optic disc and visual field changes (for details, see page 238). 3. Normal tension glaucoma (NTG) or low tension glaucoma (LTG) is diagnosed when typical glaucomatous disc cupping with or without visual field changes is associated with an intraocular pressure constantly below 21 mm of Hg (for details, see page 239). MANAGEMENT General considerations Baseline evaluation and grading of severity of glaucoma The aim of treatment is to lower intraocular pressure to a level where (further) visual loss does not occur. The management thus requires careful and regular periodic supervision by an ophthalmologist. Therefore, it is important to perform a good baseline examination with which future progress can be compared. Baseline data should include: visual acuity, slit-lamp examination of anterior segment, tonometry (preferably with applanation tonometer); measurement of central corneal thickness, optic disc evaluation (preferably with fundus photography), gonioscopy and visual field charting. Grading. American Academy of Ophthalmology (AAO) grades severity of glaucoma damage into mild, moderate and severe (Table 10.3). Therapeutic choices ■Medical therapy, ■Argon or diode laser trabeculoplasty, and ■Filteration surgery. A. Medical therapy The initial therapy of POAG is still medical, with surgery as the last resort. Antiglaucoma drugsavailable are described in detail on pages 449–453. Basic principles of medical therapy of POAG 1. Identification of target pressure. From the baseline evaluation data a ‘target pressure’ (below which Table 10.3 Severity of glaucoma damage Degree Description Mild Characteristic optic-nerve abnormalities are consistent with glaucoma but with normal visual field. Moderate Visual-field abnormalities in one hemi-field and not within 5 degrees of fixation. Severe Visual-field abnormalities in both hemi-fields and within 5 degrees of fixation. Source : AAO 2000a glaucomatous damage is not likely to progress) should be identified for each patient. The target pressure is identified taking into account the severity of existing damage, the level of IOP, age, and general health of the patient. Although, it is not possible to predict the safe level of IOP, however, progression is uncommon if IOP is maintained at less than 16 to 18 mm of Hg in patients having mild to moderate damage. Lower target pressures (12–14 mm Hg) are required in patients with severe damage. 2. Single drug therapy.One topically instilled antiglaucoma drug should be chosen after due consideration to the patient’s personal and medical factors. If the initial drug chosen is ineffective or intolerable, it should be replaced by the drug of second choice. 3. Combination therapy. If one drug is not sufficient to control IOP then a combination therapy with two or more drugs should be tried. 4. Monitoring of therapy by disc changes and field changes and tonometry is most essential on regular follow-up. In the event of progress of glaucomatous damage the target pressure is reset at a lower level. Treatment regimes There are no clear-cut prescribed treatment regimens for medical therapy of POAG. However, at present considerations are as follows: I. Single drug therapy. Antiglaucoma drugs used are: 1. Prostaglandin analogues. These decrease the IOP by increasing the uveo-scleral outflow of aqueous. Presently, a prostaglandin analogue is being considered the drug of first choice for the treatment of POAG (provided patient can afford to buy it). Further, these form a very good adjunctive drug to beta-blockers, dorzolamide and even pilocarpine when additional therapy is indicated. The available preparations include: • Latanoprost (0.005%) to be used HS, • Travoprost (0.004%) to be used HS, • Bimatoprost (0.03%, a prostamide) to be used HS, and • Unoprostone (0.15%) to be used BID. 2. Topical beta-blockers are being recommended as the first drug of choice for medical therapy of POAG in poor and average income patients. These lower IOP by reducing the aqueous secretion due to their effect on beta-2 receptors in the ciliary processes. Preparations. In terms of effectiveness, there is little difference between various beta-blockers. However, each offers a slight advantage over the other, which may help in choosing the particular medication as follows: Chapter 10 Glaucoma 237 • Timolol maleate, a non-selective beta-blocker (0.25, 0.5%: 1–2 times/day), is most popular as initial therapy. However, it should not be used in patients having associated bronchial asthma and/ or heart blocks. • Betaxolol (0.25%: 2 times/day). Being a selective beta-1 blocker it is preferred as initial therapy in patients with asthma and other pulmonary problems. • Levobunolol (0.25, 0.5%: 1–2 times/day). Its action lasts the longest and so is more reliable for once a day use than timolol. • Carteolol (1%: 1–2 times/day). It raises triglycerides and lowers high density lipoproteins the least. Therefore, it is the best choice in patients with POAG having associated hyperlipidemias or atherosclerotic cardiovascular disease. 3. Adrenergic drugs. Role in POAG is as follows: i. Epinephrine hydrochloride (0.5, 1, 2%: 1–2 times/ day) and dipivefrin hydrochloride (0.1%: 1–2 times/ day). These drugs lower the IOP by increasing aqueous outflow by stimulating alpha receptors in the aqueous outflow system. These are characterized by a high allergic reaction rate. Their long-term use has also been recognized as a risk factor for failure of filtration glaucoma surgery. For these reasons, epinephrine compounds are no longer being used as first line or second line drug. However, dipivefrine may be combined with beta-blockers in patients where other drugs are contraindicated. ii. Brimonidine (0.2% : 2 times/day). It is a selective alpha-2-adrenergic agonist and lowers IOP by decreasing aqueous production and also by increasing uveo-scleral outflow. Because of increased allergic reactions and tachyphylaxis rates it is not considered the drug of first choice in POAG. It is used as second drug of choice and also for combination therapy with other drugs. 4. Dorzolamide (2%: 2–3 times/day) or Brizolamide (1%, BD). These are topical carbonic anhydrase inhibitors which lower IOP by decreasing aqueous production by altering ion transport along the ciliary process epithelium. These have replaced pilocarpine as the second line of drug and even as an adjunct drug. 5. Pilocarpine (1, 2, 4%: 3–4 times/day). It is a very effective drug and had remained as the sheet anchor in the medical management of POAG for a long time. However, presently it is not being preferredas the first drug of choice or even as second choice. It is because of the fact that in younger patients it causes problems due to spasm of accommodation and miosis. Most, but not all, older patients tolerate pilocarpine very well; however, axial lenticular opacities when present preclude its use in many such patients. Therefore, presently pilocarpine is being considered only as an adjunctive therapy where other combinations fail and as second choice in poor patients. ■Mechanism of action. Pilocarpine contracts longitudinal muscle of ciliary body and opens spaces in trabecular meshwork, thereby mechanically increasing aqueous outflow. II. Combination topical therapy. If one drug is not effective, then a combination of two drugs—one drug which decreases aqueous production (timolol or other betablocker, or brimonidine or dorzolamide) and other drug which increase aqueous outflow (latanoprost or brimonidine or pilocarpine) may be used. III. Role of oral carbonic anhydrase inhibitors in POAG. Acetazolamide and methazolamide are not recommended for long-term use because of their side-effects. However, acetazolamide 250 mg-tds may be added to control IOP for short term. IV.Hyperosmotic agentslike mannitol 1–2 gm/kg body weight may be used initially when patients present with very high IOP ( >30 mm Hg). V. Neuroprotective agents. Neuroprotection is an IOP independent method of treating the retinal ganglion cells (RGCs) that are damaged in glaucoma. Some currently available neuroprotective agents have shown effects in vitro and in animal models, however, results in human clinical trials are either lacking or inconclusive. B. Laser trabeculoplasty Laser trabeculoplasty can be done using argon laser (ALT), or diode laser (DLT) and selective laser trabeculoplasty (SLT). It should be considered in patients where IOP is uncontrolled despite maximal tolerated medical therapy. It can also be considered as primary therapy where there is non-compliance to medical therapy. Technique and role of argon (ALT) or diode laser trabeculoplasty (DLT) inPOAG. It has an additive effect to medical therapy. Its hypotensive effect is caused by increasing outflow facility, possibly by producing collagen shrinkage on the inner aspect of the trabecular meshwork and opening the intratrabecular spaces. It has been shown to lower IOP by 8–10 mm of Hg in patients on medical therapy and by 12–16 mm in patients who are not receiving medical treatment. Treatment regime usually employed consists of 50 spots on the anterior half of the trabecular meshwork over 180°. 238 Section III Diseases of Eye Complications include: ■Transient acute rise of IOP, which can be prevented by pretreatment with apraclonidine (an alpha agonist) and/or acetazolamide; and ■Transient inflammation which can be lessened by use of topical steroids for 3–4 days. ■Other complications seen less commonly are haemorrhage, uveitis, peripheral anterior synechiae and reduced accommodation. Selective laser trabeculoplasty (SLT),based on the principle of selective photothermolysis, targets selectively pigmented trabecular meshwork (TM) cells without causing thermal or collateral damage to non-pigmented cells or structures unlike ALT or DLT. SLT is performed using Q-switched frequency doubled 532 nm Nd:YAG laser with a pulse duration of 3 ms, a spot size of 400 microns and energy setting of 0.8 mJ. Pressure lowering effect of SLT is similar to ALT with the advantage of not causing scarring and damage to TM. Further, SLT can be used in patients treated with ALT. C. Surgical therapy Indications 1. Uncontrolled glaucoma despite maximal medical therapy and laser trabeculoplasty. 2. Noncompliance of medical therapy and non-availability of ALT/SLT. 3. Failure of medical therapy and unsuitable for ALT either due to lack of cooperation or inability to visualize the trabeculum. 4. Eyes with advanced disease, i.e., having very high IOP, advanced cupping and advanced field loss should be treated with filtration surgery as primary line of management. Types of surgery Surgical treatment of POAG primarily consists of a fistulizing (filtration) surgery which provides a new channel for aqueous outflow and successfully controls the IOP (below 21 mm of Hg). • Trabeculectomy is the most frequently performed filtration surgery nowadays. • Details of filtration operations are described on page 254. OCULAR HYPERTENSION Definition Ocular hypertension is labelled when a patient has an IOP constantly more than 21 mm of Hg but no optic disc and visual field changes. These patients should be carefully monitored by an ophthalmologist and should be treated as cases of POAG in the presence of high risk factors. Glaucoma suspect is defined as an adult having normal open angle on gonioscopy and anyone of the following signs in at least one eye: • Elevated IOP, consistently more than 21 mm of Hg by applanation tonometry. • Suspicious disc changes in the form of asymmetric cup–disc ratio (difference >0.2), notching, or narrowing of neuroretinal rim, or a disc haemorrhage. • Visual fields consistent with glaucomatous damage. Risk factors for development of POAG among individuals with ocular hypertension High-risk factors for development of POAG reported by ocular hypertension study (OHTS) and European Glaucoma Prevention Study (EGPS) are; • IOP consistently >30 mm Hg, • Central corneal thickness <550 µm, • Vertical cup disc ratio of more than 0.7, • Increased age, • Increased pattern standard deviation (PSD) on Humphrey visual field test, and • Disc haemorrhages i.e., splinter haemorrhages over or near the disc. Other reported risk factors are: • Family history of glaucoma or known genetic predisposition. • Fellow eye of the unilateral POAG. • Other ocular conditions include suspicious disc appearance, myopia, positive diurnal variation, steroid responder, and low optic nerve perfusion pressure. • Systemic risk factors include diabetes mellitus, sleep apnea, hypertension, cardiovascular disease, hypothyroidism, migranous headache and vasospasm. Note. The risk of developing POAG cannot be predicted from a single risk factor. The multivariate analysis of the risk factors is more useful in predicting the development of POAG in glaucoma suspects. Treatment • Patients with high-risk factors should be treated on the lines of POAG (see page 236). The aim should be to reduce IOP by 20%. • Patients with no high-risk factors should be annually followed by examination of optic disc, perimetry and record of IOP. Treatment is not required till glaucomatous damage is documented. Chapter 10 Glaucoma 239 NORMAL TENSION GLAUCOMA Definition and prevalence The term normal tension glaucoma (NTG), also referred to as low tension glaucoma is labelled when typical glaucomatous disc changes and visual field defects are associated with an intraocular pressure (IOP) constantly below 21 mm of Hg. Characteristically, the angle of anterior chamber is open on gonioscopy and there is no secondary cause for glaucomatous disc changes. NTG accounts for 16% of all cases of POAG and its prevalence above the age of 40 years is 0.2%. Etiopathogenesis It is believed to result from chronic low vascular perfusion, which makes the optic nerve head susceptible to normal IOP. This view is supported by following associations which are more common in NTG than in POAG: • Raynaud phenomenon, i.e., peripheral vascular spasm on cooling, • Migraine, • Nocturnal systemic hypotension and overtreated systemic hypertension. • Reduced blood flow velocity in the ophthalmic artery (as revealed on transcranial Doppler ultrasonography). Clinical features Intraocular pressure (IOP) is consistently lower than 21 mm of Hg, but is usually on the higher side of normal range. Optic disc changesare similar to POAG with following special features: • Thinning of neuroretinal rim is more significant. • Splinter haemorrhages at disc are more frequent. • Peripapillary atrophic changes are more prevalent. Visual field defects are essentially similar to POAG, but tend to be more deeper, steeper, more localized and closure to fixation point. Characteristic associations in the form of ocular vascular abnormalities and systemic vascular and hematological abnormalities (as mentioned in etiopathogenesis) may be detected. Differential diagnosis I. High pressure glaucomas 1. POAG. In early stages. POAG may present with normal IOP because of a wide diurnal variation. Diurnal variation test usually depicts IOP higher than 21 mm of Hg at some hours of the day in patients with POAG. 2. Glaucoma with intermittent rise in IOP, e.g., glaucomatocyclitic crisis and intermittent angle closure glaucoma. 3. Previous episodes of glaucoma which might have caused optic disc changes, field defects, and are now cured, e.g., corticosteroid induced glaucoma, uveitic glaucoma, and traumatic glaucoma. II. Non-glaucomatous optic neuropathies 1. Congenital optic disc anomalies such as large optic disc pits or colobomas which may be mistaken for acquired glaucomatous damage. A careful examination should help in differentiation. 2. Acquired optic neuropathies such as compressive lesions of optic nerve, shock optic neuropathies, anterior ischemic optic neuropathy, traumatic optic neuropathy and optic neuropathy due to methyl alcohol poisioning. Treatment 1. Medical treatment to lower IOP. The aim of the treatment is to lower IOP by 30%, i.e., to achieve IOP levels of about 12–14 mm of Hg. Some important facts about medical treatment of NTG are: • Betaxolol may be considered the drug of choice because in addition to lowering IOP it also increases optic nerve blood flow. • Other beta blockers and adrenergic drugs (such as dipivefrine) should better be avoided (as these cause nocturnal systemic hypotension and are likely to affect adversely the optic nerve perfusion). • Drugs with neuroprotective effect like brimonidine may be preferred. • Prostaglandin analogues, e.g., latanoprost tend to have a greater ocular hypotensive effect in eyes with normal IOP. 2. Trabeculectomymay be considered when progressive field loss occurs despite IOP in lower teens. 3. Systemic calcium channel blockers (e.g., nifedipine) may be useful in patients with confirmed peripheral vasospasm. 4. Monitoring of systemic blood pressure should be done for 24 hours. If nocturnal dip is detected, it may be necessary to avoid night dose of anti-hypertensive medication. PRIMARY ANGLE-CLOSURE DISEASE TERMINOLOGY Since in the new classification, described of ‘Association of International Glaucoma Societies’ (AIGS), in 2006, the word glaucoma is used only when the optic disc and visual field changes are present, so the term ‘primary angle closure disease’ should replace the term ‘primary angle closure glaucoma’. Primary angle closure disease, is characterised by apposition of peripheral iris against the trabecular 240 Section III Diseases of Eye meshwork (TM) resulting in obstruction of aqueous outflow by closure of an already narrow angle of the anterior chamber. The condition is not associated with any other ocular and systemic abnormalities. EPIDEMIOLOGY Salient points regarding epidemiology of primary angle closure disease as per International Society of Geographical and Epidemiological Ophthalmology (ISGEO) are as below: 1. For every 10 occludable angles (PAC suspects) seen there is only one case of PACG. Thus, most occludable eyes do not get glaucoma; and so does not justify prophylactic Laser P.I. in all such cases. 2. Chronic PACG (asymptomatic) is more common than acute PACG (symptomatic) (3:1); meaning thereby that most patients do not know they have disease; justifying need for glaucoma screening. 3. There is great ethnic variability in the prevalence of PACG. The ratio of POAG versus PACG reported for different ethnic groups is as below: Ethnic group POAG : PACG Europeans, and Africans and Hispanics : 5 : 1 Urban Chinese : 1 : 2 Mongolian : 1 : 3 Indian : 1 : 1 4.Major cause of world glaucoma blindness is PACG. ETIOPATHOGENESIS Etiopathogenesis of primary angle closure disease can be discussed as below: A. Predisposing risk factors B. Pathogenesis of rise in IOP A. Predisposing risk factors I. Demographic risk factors 1.Age. PACG with pupillary block occurs with greatest frequency in 6th and 7th decades of life. 2.Gender. Male to Female ratio is 1:3. 3.Race. In Caucasians, PACG accounts for about 6% of all glaucomas and presents in sixth to seventh decade. It is more common in South-East Asians, Chinese and Eskimos but uncommon in Blacks. In Asians it presents in 5th to 6th decade and accounts for 50% of primary adult glaucomas in this ethnic group. II. Anatomical and ocular risk factors Eyes anatomically predisposed to develop primary angle-closure glaucoma (PACG) include: • Hypermetropic eyes with shallow anterior chamber and short axial length. • Eyes in which iris-lens diaphragm is placed anteriorly. • Eyes with narrow angle of anterior chamber, which may be due to small eyeball, relatively large size of the lens and smaller diameter of the cornea or bigger size of the ciliary body or more anterior insertion of the iris on the ciliary body. • Plateau iris configuration. • Heredity. Most cases of PACG with pupillary block are sporadic in nature. However, predisposing anatomical factors, i.e., shallow anterior chamber and narrow angles have been reported as more common in first degree relatives of the patients. B. Pathomechanisms of ‘rise in intraocular’ pressure Three pathomechanisms implicated in the causation of rise in IOP of the eyes at risk of PACG are: ■Pupillary block mechanism, ■Plateau iris configuration and syndrome, and ■Phacomorphic mechanism. 1. Pupillary block mechanism Pupillary block mechanism is responsible for causation of rise in IOP in most (70%) of the predis-posed patients. Precipitating factors. In a predisposed patient with occludable angles the pupillary block causing angle closure is precipitated by the following factors: ■Physiological mydriasis e.g., while reading in dim illumination, watching television or cinema in a darkened room, during anxiety and emotional stress (sympathetic overactivity) ■Pharmacological mydriasis is well documented to precipitate an attack of acute angle closure. Medications other than topical mydriatics (e.g., phenylephrine, tropicamide, cyclopentolate, homatropine and atropine) reported to precipitate the attack include tranquilizers, bronchodilators, antidepressants, vasoconstrictors including common nasal decongestants, antimalaria agents and antispasmodics. ■Pharmacological miosis induced by drugs like echothiophate and pilocarpine is also reported to precipitate an attack of acute PAC. ■Valsalva manoevure is reported to precipitate angle closure in predisposed individuals. Mechanism of rise in IOP after mydriasis.The probable sequence of events resulting in rise of IOP in an anatomically predisposed eye is as follows: First of all due to the effect of precipitating factors there occurs mid dilatation of the pupil which increases the amount of apposition between iris and anteriorly placed lens with a considerable pressure resulting in relative pupil block (Fig. 10.16A). Consequently, the aqueous collects in the posterior chamber and pushes the peripheral flaccid Chapter 10 Glaucoma 241 iris anteriorly (Iris bombe) (Fig. 10.16B), resulting in appositional angle closure due to iridocorneal contact (Fig. 10.16C). Eventually, there occurs rise in IOP which is transient to begin with. But slowly the appositional angle closure is converted into synechial angle closure (due to formation of peripheral anterior synechiae) and an attack of rise in IOP may last long. In some cases, a mechanical occlusion of the angle by the iris is sufficient to block the drainage of aqueous. For this reason, the instillation of atropine in an eye with a narrow angle is dangerous, since it may precipitate an attack of raised IOP. Mechanism of rise in lOP after miosis. The drugs that constrict pupil are also reported to increase pupillary block. Further these drugs also contract the ciliary muscles allowing the zonules to relax and the lens to move forward. Because of this reason, it is advisable to avoid miotics such as pilocarpine in the prevention of PACG in predisposed eyes (e.g., fellow eye of patient with acute attack). 2. Plateau iris configuration and syndrome This mechanism is responsible for few (10%) atypical cases of acute angle closure glaucoma. Acute angle closure glaucoma associated with plateau iris is atypical in the patients that have normal central A B C Fig. 10.16 Mechanism of angle closure glaucoma: A, relative pupil block; B, iris bombe formation; C, appositional angle closure anterior chamber depth, flat iris plane and minimal pupillary block. It has also been referred in the literature as an angle closure glaucoma without pupillary block. The anterior chamber angle is closed by a pushing mechanism because of the anterior positioned ciliary processes displacing the peripheral iris anteriorly. Such a situation is called plateau iris configuration and iridotomy is sufficient to control IOP in such patients. Plateau iris syndrome is labeled when acute angle closure glaucoma occurs either spontaneously or after pharmacological dilation, in spite of patent iridotomy. Such eyes are treated with miotics and laser peripheral iridoplasty to produce thinning of the peripheral iris. 3. Phacomorphic mechanism Phacomorphic mechanism has now been included as one of the three basic PACG mechanisms, along with pupillary block and plateau iris. The abnormal lens may contribute by either causing pupillary block or by pushing the peripheral iris forward into the angle structures. Though the term phacomorphic glaucoma refers to an acute secondary angle closure glaucoma caused by the intumescent or other lens morphological abnormalities; but now UBM and OCT studies have shown that phacomorphic mechanism may be responsible for initiating acute primary angle closure glaucoma in predisposed patients (having occludable angle). This also forms the base of lens extraction as a treatment modality for acute primary angle closure glaucoma. Note. In addition to meticulous gonioscopic examination, the high resolution ultrasonic biomicroscopy (UBM) examination and Anterior Segment OCT (AS-OCT) are very useful in understanding the pathogenesis of primary angle closure disease. These investigations are particularly useful in the documentation of plateau iris configuration, plateau iris syndrome, phacomorphic mechanism and post peripheral iridectomy angle dynamics. Further, these investigations are also helpful in differentiating primary and secondary angle closure glaucoma. CLASSIFICATION ISGEO Classification World glaucoma experts under the auspices of the “Association of International Glaucoma Societies” (AIGS), now termed as ‘International Society of Geographical and Epidemiological Ophthalmology’(ISGEO), in 2006 have proposed following 21st century consensus classification based on natural history(IOP measurements, gonioscopy, disc and visual field evaluation): 242 Section III Diseases of Eye 1.Primary Angle Closure Suspect (PACS), 2.Primary Angle Closure (PAC), and 3.Primary Angle Closure Glaucoma (PACG). Note. In this newer classification the word glaucoma is used only when the optic disc changes and field changes are present. Further, this classification is based only on the signs and has not taken into consideration the presenting symptoms. Traditional clinical classification The old traditional clinical classification based on the clinical presenting symptoms is as below: 1.Latent primary angle-closure glaucoma, 2.Subacute (intermittent) primary angle-closure glaucoma, 3.Acute primary angle-closure glaucoma, and 4.Chronic primary angle-closure glaucoma. CLINICAL PROFILE AND MANAGEMENT Clinical profile of three stages of primary angle-closure disease described below is based on the integration of the new ISGEO classification (based on natural history) with traditional clinical classification (based on the presenting symptoms). I. Primary Angle-Closure Suspect Primary angle-closure suspect (PACS), can be considered analogous to the term ‘latent primary angle-closure glaucoma’ of clinical classification. Clinical features and diagnostic criteria Symptoms are absent in this stage. Presenting situations for diagnosis include: • Suspicious clinical signs on routine ocular examination in patients coming for some other complaints. • Fellow eye of the patients presenting with acute attack of PAC. • Glaucoma screening programme. Suspicious clinical signs noted on routine ocular examination include: 1. Eclipse sign. Eclipse sign, which indicates decreased axial anterior chamber depth, can be elicited by shining a penlight across the anterior chamber from the temporal side and noting a shadow on the nasal side (Fig. 10.17). 2. Slit-lamp biomicroscopic signs include: • Decreased axial anterior chamber depth, • Convex shaped iris lens diaphragm, and • Close proximity of the iris to cornea in the periphery. 3. Van Herick slit-lamp grading of the angle may be used with a fair accuracy. Here, the peripheral anterior A B Fig. 10.17 Estimation of anterior chamber depth by oblique illumination: A, normal; B, shallow chamber depth (PACD) is compared to the adjacent corneal thickness (CT) and the presumed angle width is graded as follows (Fig. 10.18): • Grade 4 (Wide open angle): PACD = 3/4 to 1 CT • Grade 3 (Mild narrow angle): PACD = 1/4 to 1/2 CT • Grade 2 (Moderate narrow angle): PACD = 1/4 CT • Grade 1( Extremely narrow angle): PACD < 1/4 CT • Grade 0 (closed angle): PACD = Nil Diagnostic tests recommended to confirm diagnosis include: ■IOP measurement, ■Gonioscopy, ■Ultrasonic biomicroscopy (UBM), ■Anterior segment OCT, ■Optic disc evaluation, and ■Visual field analysis. Diagnostic criteria for PAC suspect: ■Gonioscopy should reveal irido-trabecular contact in greater than 270° angle and no peripheral anterior synechia (PAS absent). ■IOP should be normal. ■Optic disc should show no glaucomatous change. ■Visual fields should be normal. Impression: The angle is at risk. Chapter 10 Glaucoma 243 Fig. 10.18 Van Herick method of slit-lamp grading of angle width: A, Grade IV; B, Grade III; C, Grade II; and D, Grade I, and E Grade 0. PACD = Peripheral anterior chamber depth; CT = Corneal thickeners Management Provocative tests designed to precipitate closure of the angle though not popular presently but can be performed in patients with PAC suspect. These tests may be performed in the ophthalmologist’s office, where it can be treated promptly. 1. Prone-darkroom test was considered the most popular and best physiological provocative test. In this test, baseline IOP is recorded and patient is made to lie prone in a darkroom for 1 hour. He must remain awake so that pupils remain dilated. After 1 hour, the IOP is again measured. An increase in IOP of more than 8 mm Hg is considered diagnostic of PAC suspect. 2. Mydriatic provocative test is usually not preferred nowadays because this is not physiological. In this test either a weak mydriatic (e.g., 0.5% tropicamide) or simultaneously a mydriatic and miotic (10% phenylephrine and 2% pilocarpine) are used to produce a mid-dilated pupil. A pressure rise of more than 8 mm Hg is considered positive. Inferences from provocative tests are: • Positive provocative test indicates that angle is capable of spontaneous closure. • Negative provocative test in the presence of occludable angles on gonioscopy does not rule out a possibility of spontaneous closure. So, patient should be warned of possible symptoms of an acute attack of PAC. Treatment comprise: Prophylactic laser iridotomy is warranted if more than 270° of oppositional iridotrabecular contact is seen on gonioscopy in the fellow eye of all patients presenting with acute PAC or PACG in one eye. If untreated, the risk of conversion to PACG during the next 5 years is about 50%. Periodic follow up. Patients with PAC suspect in both eyes need to be followed periodically and educated about the symptoms of the disease. II. Primary Angle-Closure Eyes with primary angle closure (PAC) may be considered to comprise following entities of clinical classification: • Subacute primary angle closure • Acute PAC • Chronic PAC (asymptomatic). Defining criteria for primary angle closure (PAC) • Irido-trabecular contact noted on gonioscopy in greater than 270° angle, • IOP elevated and/or peripheral anterior synechiae (PAS) present, • Optic disc: Normal, and • Visual fields: Normal Impression: Angle is abnormal either in function (elevated IOP) and/or structure (PAS +ve). 244 Section III Diseases of Eye Subacute primary angle-closure Subacute primary angle closure is characterized by an attack of transient rise of IOP (40–50 mm Hg) which may last for few minutes to 1–2 hours. Precipitating factor such an attack in a patient with PAC include: ■Physiological mydriasis e.g., while reading in dim illumination, watching television or cinema in a darkened room, or during anxiety (sympathetic overactivity); or ■Physiological shallowing of anterior chamber after lying in prone position. ■Pharmacological mydriasis following use of pupil dilating drugs for fundus examination. Symptoms include: ■Episode of subacute PAC is marked by experience of unilateral transient blurring of vision, ■Coloured halos around light, headache, browache and eyeache on the affected side. ■Self-termination of the attack occurs possibly due to physiological miosis induced by bright light, sleep or otherwise. ■Recurrent attacks of such episodes are not uncommon. Between the recurrent attacks the eyes are free of symptoms. Signs. Usually, during examination the eye is white and not congested. However, all the signs described above in the definition of primary angle-closure (PAC) should be elicited to table PAC. Diagnosis is made from the defining criteria for PAC as above. Differential diagnosis of coloured halos in PAC. Coloured halos during intermittent attacks of raised IOP in PAC occur due to accumulation of fluid in the corneal epithelium and alteration in the refractive condition of the corneal lamellae. Patient typically gives history of seeing colours distributed as in the spectrum of rainbow (red being outside and violet innermost) while watching on a lighted bulb or the moon. The coloured halos in glaucoma must be differentiated from those found in acute purulent conjunctivitis and early cataractous changes. In conjunctivits, halos can be eliminated by irrigating the discharge. The halos of glaucoma and immature cataract may be differentiated by Fincham’s test in which a stenopaeic slit is passed across the pupil. During this test, glaucomatous halo remains intact, while a halo due to cataract is broken up into segments (Fig. 10.19). Treatment of choice is Peripheral laser iridotomy. Acute primary angle-closure An attack of acute rise in IOP in patients with primary angle closure (PAC) may occur due to pupillary block causing sudden closure of the angle. It usually does not terminate of its own and thus if not treated lasts for many days. It is a sight threatening emergency. Clinical features Symptoms include: ■Pain.Typically acute attack is characterised by sudden onset of very severe pain in the eye which radiates along the branches of 5th nerve. ■Nausea, vomiting and prostrations are frequently associated with pain. ■Rapidly progressive impairment of vision, redness, photophobia and lacrimation develop in all cases. ■Past history. About 5% patients give history of typical previous intermittent attacks of subacute angle-closure. A B C D E Fig. 10.19 Emsley-Fincham stenopaeic-slit test demonstrating breaking up of halos due to immature cataract into different segments Chapter 10 Glaucoma 245 Signs include (Fig. 10.20): • Lids may be oedematous, • Conjunctiva is chemosed, and congested, (both conjunctival and ciliary vessels are congested), • Cornea becomes oedematous and insensitive, • Anterior chamber isvery shallow. Aqueous flare or cells may be seen in anterior chamber, • Angle of anterior chamber is completely closed as seen on gonioscopy (Shaffer grade 0), • Iris may be discoloured, • Pupil is semidilated, vertically oval and fixed. It is non-reactive to both light and accommodation, • IOP is markedly elevated, usually between 40 and 70 mm of Hg, • Optic disc is oedematous and hyperaemic, • Fellow eye shows shallow anterior chamber and occludable angle. Diagnosis Diagnosis of an attack of acute primary angle closure is usually obvious from the clinical features. However, a differential diagnosis may have to be considered: 1.From other causes of acute red eye. Acute primary angle closure sometimes needs differentiation from other causes of inflammed red eye like acute conjunctivitis and acute iridocyclitis (see page 158 and Table 8.1). 2.From acute secondary glaucomas such as: • Phacomorphic glaucoma (see page 248), • Acute neovascular glaucoma (see page 250) and • Glaucomatocyclitic crisis (see page 169). Management Acute angle closure is a serious ocular emergency and needs to be managed aggressively as below: • Immediate medical therapy to lower IOP, • Definitive treatment, • Prophylaxis of the fellow eye, and Fig. 10.20 Clinical photograph of a patient with acute congestive glaucoma. Note ciliary congestion, corneal oedema and mid-dilated pupil