LUMINOUS RETINA

Luminous Retina

As we have seen in the previous material, we will illuminate the fundus with the retinoscope and observe rays coming from the retina, as if it were luminous. When light leaves the retina, the optical system of the eye applies vergence to the rays. If we illuminate the retina with parallel rays (plane mirror), the reflected rays leave the eye according to the refractive error.* That is: In emmetropia, rays leave parallel. In hyperopia, rays leave diverging. In myopia, rays leave converging. This backward approach may seem confusing at first, but simplifies understanding of the retinoscopic reflex. Things happen differently when we illuminate the retina with rays that are not parallel, but we will ignore these for now. In visualizing the situation, we will use a graphic presentation to illustrate luminous retina optics in three basic situations: emmetropia (plano), hyperopia (+1 D), and myopia (–1 D). Since the rays entering the eye remain parallel in all cases, we will ignore them entirely and simply look at what emerges. This is a very graphic presentation, so study and compare the diagrams carefully. Figure 4-1 offers one more way of looking at the FP optics . We see the emmetropic FP at infinity, the hyperope’s FP beyond infinity, and the myope’s FP at less than infinity. Figure 4-1. Rays from the illuminated retina. Correction refers to the lens desired to correct the refractive error. Now, picture yourself sitting before each of the eyes in Figure 4-2. Looking through the peephole in your retinoscope, you see these emerging rays as a red reflex in the patient’s pupil. If you sweep the streak across the eye, the reflex you see will also move. If the emerging rays have not converged to a point (the FP), the retinal reflex will move in the same direction as you move the streak; this is called the with motion reflex (WITH). If the rays have come to the FP and diverged, the reflex will move opposite to your movements; this is the against motion reflex (AGAINST) (see Figure 4-2).† Figure 4-2. Retinal reflex movement. Note movement of the streak from face and from retina in WITH versus AGAINST motion. Now picture yourself sitting almost at infinity looking through your retinoscope. This is what you would see in each of the three cases (Figure 4-3). In the emmetrope and hyperope, the emerging rays have not converged to the FP, so you see WITH motion. In the –1 myope, the rays have come to a focus at the FP (1 meter) and have diverged; thus, you would see AGAINST motion. Figure 4-3. Retinoscopy at infinity. Note that within the FP, you see WITH motion; beyond the FP, you see AGAINST motion. Consider this situation another way: if you see AGAINST, you are beyond the FP; if you see WITH, the FP is beyond you! So much for what you would see if you sat at infinity. Optical infinity is anywhere beyond 6 meters (20 feet), but you cannot reasonably sit that far away: the reflex would be too dull, and you cannot place correcting lenses before the eye. But if you sit at 1 meter, the reflex appears brighter, and you can (almost) reach the patient conveniently (Figure 4-4).  Retinoscopy at one meter. Note that the FP of the 1 D myope (–1) is at 1 meter. With your scope 1 meter from the patient, you would still see WITH, but in the case of the emmetrope and hyperope, their FPs are beyond you. However, in the case of the 1 D myope (FP at 1 meter), you would see a different reflex: if you leaned forward, you would now see WITH; if you tilted backward, you would see AGAINST. But when you sit with your retinoscope right at the FP of the eye, you see the neutrality reflex (Figure 4-5). . Neutrality reflex (NEUT) FP conjugate with the peephole of the retinoscope. When you are at the FP, the pupil floods with light. There is no streak reflex and no movement WITH or AGAINST. The retina of the eye is conjugate with the peephole of the retinoscope. Since the reflex reverses itself (ie, changes from WITH to AGAINST motion) at the FP, some call neutrality the reversal point.

OPTICS AND REFRACTION

The Schematic Eye : Auxiliary Lenses and Vertex Distance

We will use auxiliary trial lenses to create refractive errors greater than those obtainable by changing the length of the schematic eye. We call these phantom lenses, and they sit in the rack in front of the eye. These lenses create an ametropia of equal power but opposite sign; that is, plus lenses create a myopicerror and minus lenses a hyperopic error. The power of the phantom is added to the setting of the schematic eye. For example, if you set the scale at –2 D and put a +10 D phantom before the eye, the combination would simulate a myopia of –12 D. The +10 D phantom simulates a 10 D myopia by converging retina rays to the myopic FP of 10 cm. We also use auxiliary lenses to correct refractive errors, as you have already seen. To correct an ametropia, we add lenses of appropriate sign and power, with allowance for our working distance. Problems arise, however, in creating or correcting errors when you stack several lenses together. Thenominal power of a lens (marked on the handle) presumes a short vertex distance (the distance between the back of the lens and the front of the cornea). The effective power changes as the vertex distance (VD) increases. The difference is slight with weak lenses, but increases dramatically as the lenses become stronger. As a rule of thumb, the effective power of a strong lens (±10 D) changes about 1% for each millimeter it is moved. The power of a 10 D lens moved 10 mm changes by about 1 D.† When you increase the VD, pluslenses get stronger (effective power increases) and minus lenses become weaker (effective power decreases). Since effective power relates to VD, make it a habit to keep the strongest lenses closest to the eye. It is especially important to be aware of this change in effective lens power when working with the schematic eye, where the distance between the front and rear cells may be as much as 25 mm. Thus, on some models, the effective power of a strong lens changes by 25% when it is moved from the rear to the front cell. Obviously, you will want to keep the lenses close together. However, errors will still creep in when using strong lenses, and failure to appreciate this leads to a lot of unnecessary weeping. Since the distance between cells is at least 5 mm, a –10 D phantom in the rear cell is slightly overcorrected by a +10 D lens in the next cell. With lens power less than +3 D, the effect between adjoining cells is insignificant. Thankfully, refracting machines have vertex compensation to prevent all these errors. You will only need to consider the VD of the machine itself (compared to the VD of the spectacles) in writing the final prescription. As if this were not enough, each additional lens gives two more surface reflections for you to cope with. Each lens also reduces the brightness of the reflex, since the light has been refracted four times in the two-way path through the lens. Always use the fewest lenses to achieve a desired result; for example, replace a stack consisting of +1.50 D, +0.75 D, and +0.25 D lenses with a +2.50 D lens. You will have problems with your schematic eye in the pages ahead; everyone does, but you will catch on. Be a little forgiving of its calibration and inconsistencies; it is imperfect, but it will teach you fundamentals. By the time you are truly thwarted by the model eye’s limitations, you will be ready to retinoscope patients. Since many of you may already be employed in an ophthalmic office, or have access to an eye refracting lane, I’ve asked Rich Reffner to explain his teaching method. He uses a refractor in retinoscopy of the training eye.

                   Phthisical globe:

A 29 year-old sustained a rupture right globe in a motor bike accident 2 years ago and despite repair, the globe became severely phthisical with a significant loss of orbital volume. Despite an ocular prosthesis, the right eye appears enophthalmos. She wishes to improve her appearance. Surgery to increase the orbital volume is planned by performing an enucleation and simultaneous orbital implant. The prosthesis also needs to be changed to complement the iris colour of the good eye.

                   :MACULAR HOLES:

Rajesh.Dodda

The treatment of macular holes has progressed substantially in the past decade. Traumatic macular holes provide a unique challenge, especially when they are of long-standing duration. Certainly the goal of macular hole surgery in general is to improve visual acuity. This can be difficult, however, in the context of chronic macular holes due to secondary retinal pigment epithelial atrophy. Nonetheless, surgery may help relieve particular visual disturbances associated with macular holes, such as symptomatic central scotomas. Recently, we were able to successfully close a macular hole extant for 25 years.

History and surgery:

A 48-year-old incarcerated African-American man complained of a “gray spot” in his right eye central vision for 25 years after sustaining blunt trauma. His left eye sustained a traumatic cataract, which was extracted and replaced with an anterior chamber IOL. Best corrected visual acuity in the right eye was count fingers at 2 feet (eccentric) and 20/20 in the left eye. Amsler grid in the right eye revealed a central scotoma of 25 × 25 mm. Slit lamp biomicroscopy was notable for a clear lens in the right eyeand an anterior chamber IOL in the left eye. Funduscopic examination of the right eye revealed a stage 3 full-thickness macular hole (Figure 1). There was retinal pigment epithelial (RPE) atrophy within and surrounding the hole. Results of funduscopic examination of the left eye were normal. Because the patient was disturbed by the central scotoma in his right eye, we offered surgery and counseled him extensively regarding risks, benefits and alternatives. Specifically, given the long-standing nature of the macular hole, we informed the patient that while his visual acuity might not improve, his central scotoma could resolve.

We performed a standard 23-gauge, three-port core vitrectomy. The posterior hyaloid face was stained with Kenalog (triamcinolone acetonide, Bristol-Myers Squibb) and detached. Diluted indocyanine green was used to stain the internal limiting membrane (ILM) in the macular area, and continuous rhexis of the ILM around the macular hole was performed. Complete fluid-air exchange was performed and 0.1 mL of autologous platelets were injected, overlying the macular hole. Air was then replaced with 14% C3F8 gas. The first postoperative day revealed platelets filling the macular hole. Two months postoperatively, the patient’s visual acuity improved to 20/200 and Amsler grid revealed resolution of the scotoma. Funduscopic examination of the right eye showed that the macular hole was closed (Figure 2). The patient was pleased with the newfound vision in his right eye.

Figure 2: At 2 months postop, the macular hole is closed.

Discussion

Closure of macular holes may be due to several factors. Previous histopathologic and electron microscopic examinations in eyes with idiopathic macular holes have shown collapse of the hole allowing for juxtaposition of the edges. Additionally, proliferated glial cells may also serve to close holes by bridging the neurosensory retinal gap. During surgery for macular holes, detachment of the posterior hyaloid face is thought to relieve anteroposterior traction, thereby favoring subsequent hole closure. The exact mechanism of traumatic macular hole formation is not known, but it is thought that contusional contrecoup forces cause anteroposterior vitreous traction upon the macula.

Chronic traumatic macular holes are considered more challenging to successfully close than acutely formed senile holes. Some surgeons employ posterior hyaloid separation and instill TGF-beta 2 into the hole, while others use autologous platelet concentrate, similar to our own experience. At least in terms of idiopathic macular holes, it is generally felt that closing holes of less than 3 years’ duration leads to better anatomic and functional endpoints than does closing older holes. Traumatic macular holes, on the other hand, are less well characterized in terms of injury-to-operating-room interval. Additionally, the best surgical technique for these cases has not been defined.

ILM peeling in idiopathic macular holes has been reported to have higher anatomical closure rates. Closure of the macular hole with subsequent improvement of macular configuration does not necessarily correlate with improved visual acuity, but scotomata may be improved with hole closure, as in our patient. Autologous platelets have been suggested to improve macular hole closure perhaps by virtue of growth factors that are inherent to the isolate. Two factors led us to combine ILM peeling with autologous platelets. Because our patient was an inmate, there was concern that maintaining strict posturing would be challenging; a prolonged period of strict bed rest in a prone position is simply not feasible in a prison setting. The second factor was that in such a long-standing traumatic macular hole, we wanted to ensure the best possible chance for hole closure. ILM peeling afforded the best opportunity to allow for anatomical closure, while autologous platelets afforded provision for growth factors that could be potentially useful during the anatomical process of closure.

The visual rehabilitation for a chronic traumatic macular hole, as our case illustrates, involves improvement of visual acuity, reduction in the size of the associated central scotoma or both. The RPE atrophy that can accompany chronic traumatic macular holes may make gains in visual acuity difficult, but other troubling visual phenomena associated with macular holes such as central scotomas might be improved with surgical intervention. Using surgical techniques such as ILM peeling and adjuvants, including platelet isolates, as was our approach in this case, may offer the best opportunity to attain satisfactory anatomical closure and, more importantly, subjective improvement in patient quality of life.

atrophic retinal hole:

RAJESH.DODDA

Disease

 An atrophic retinal hole is a break in the retina not associated with vitreoretinal traction.

Etiology and Risk Factors

Idiopathic atrophic retinal hole is the most common presentation. There are no generally accepted risk factors for this condition but lesions have been cited more often in younger myopic patients. It has been estimated about 5% of the general population has atrophic holes. Atrophic holes often present in the peripheral (temporal or superior) retina. There appears to be no sex predilection.

General Pathology

Atrophic retinal holes are full thickness retina breaks often existing in the peripheral retina. They are the result of atrophic changes within the sensory retina that are not induced by vitreous adhesions. Often, these lesions are found in association with lattice degeneration. The incidence of this associated has been reported as high as 43%.

Pathophysiology

Retinal holes are the result of chronic atrophy of the sensory retina. These lesions often take a round or oval shape. It has been postulated that the pathogenesis of this lesion stems from an atrophic pigmented chorioretinapathy that is associated with retinal vessel sclerosis and a disturbance of the overlying vitreous. As the blood supply to the retina is shut down, the retinal tissue subsequently dies in conjunction with degeneration of the surrounding vitreous. This pathology precludes traction of the vitreous to the underlying sensory retina.

Primary prevention

There are no preventative measures to the development of atrophic retinal holes.

Diagnosis

This is a clinical diagnosis based on history and clinical exam, including slit lamp and dilated fundus examination.

History

Patients with atrophic retinal holes generally present for routine ocular examinations. This type of lesion is generally an incidental finding. Some patients may present with a complaint of photopsias (flashing lights) or other visual disturbance if associated with a symptomatic retinal detachment.

Physical examination

Slit lamp examination with special attention to the peripheral fundus is important in the evaluation of this disorder. An indirect ophthalmologic examination with scleral depression may be required to indentify retinal holes adjacent to the ora serrata.
Careful attention should be used when examining myopic patients and those patients with lattice degeneration due to the increased incidence in these populations. 

Signs

Retinal holes are full thickness breaks in the sensory retina. As mentioned prior, they take a round or oval shape. Subretinal fluid may accompany these lesions. Subretinal fluid, if present, may involve up to 360 degrees of the lesion's edge and spread slowly under the surrounding retina resulting in either a symptomatic or asymptomatic retinal detachment.

Symptoms

Atrophic holes are asymptomatic in a majority of patients. If associated with a retinal detachment patients may experience visual symptoms such as photopsias, floaters, or loss of visual field.

Clinical diagnosis

The diagnosis of an atrophic retinal hole is a clinical one. There are no studies currently used to diagnose or classify this type of retinal pathology. To differentiate this lesion from an operculated retinal hole, a clinician needs to look for an isolated detachment of the sensory retina adherent to the overlying vitreous without traction to the edges of the retinal hole. The absence of vitreoretinal traction and a free retinal flap will also assist in differentiating this lesion from a horseshoe retinal tear.

Diagnostic procedures

Atrophic retinal holes are diagnosed during routine clinical examination. Depending on how far into the peripheral retina the lesions are located a clinician has the option of using either direct or indirect ophthalmoscopy.
Direct ophthalmolscopy utilizes a slit lamp for the examination and the choice of either a 78 or 90 diopter lens versus a Goldmann triple mirror lens. The 78 and 90 diopter lens provides an image of the retina which is best for viewing the posterior pole of the fundus. A skilled physician can often times manipulate the slit lamp and provide patient direction which allows for a good view of the peripheral fundus. The Goldmann triple mirror lens is designed specifically to allow for a broader view of the fundus to include the posterior pole and extend out to the ora serrata and ciliary body.

Laboratory test

No laboratory tests are indicated in cases of atrophic retinal holes.

Differential diagnosis

The clinical appearance of atrophic retinal holes is very characteristic. Despite this there are several possible diagnoses that should be considered which include horseshoe retinal tear, lattice degeneration, operculated retinal hole, snailtrack degeneration, and retinoschesis.

Management

General treatment

There is no mandatory therapy for this condition. According to the Preferred Practice Patterns set forth by the American Academy of Ophthalmology, for atrophic retina holes treatment is rarely recommended. Some studies suggest that prophylactic laserpexy may be considered for eyes with retinal holes with accompanying subretinal fluid when a retinal detachment already exists in the patient’s fellow eye.

Medical therapy

There is currently no medical therapy required for this conditonal.

Surgery

Surgical procedures (laserpexy) are rarely recommended for this condition. See above

Prognosis

The prognosis for atrophic retinal holes is good. There is a low risk of retinal detachments in patient with round holes, and the incidence of atrophic holes in the general population is low as well.

Retinal Holes and Tears

View imageWhat are retinal holes and tears?Retinal holes and tears are small breaks in the retina. The retina is the lining at the back of the eye that senses light coming into the eye. Usually holes and tears do not mean you will have serious vision problems right away. However, retinal holes and tears may cause problems if they allow fluid from the vitreous (the clear gel in the center of the eyeball) to seep behind the retina. If a lot of fluid gets behind the retina, the retina can separate from the wall of the eye. The detached part of the retina will not work properly. Detachment of the retina is a serious condition that can lead to blindness and must be treated promptly to protect as much vision as possible.What is the cause?When we are first born, the gel in the center of the eyeball called the vitreous, is entirely clear and uniform. As we age, the vitreous gel develops pockets of fluid. When a pocket of fluid develops in the very back of the eye, the vitreous can pull away from the retina. This eventually happens to everyone, and is not itself dangerous. However, sometimes the vitreous may pull on a thin or weak area of the retina, and cause a tear or hole.Problems that may increase the risk of retinal holes and tears in an eye include:

• nearsightedness

• eye injuries

• cataract or certain other types of eye surgery

• a history of retinal holes or tears in your other eye

This condition may run in families.What are the symptoms?Sometimes retinal holes and tears have no symptoms. However, the sudden appearance of many floaters (spots or squiggles before your eyes) or flashes (flickers or arcs of light in the peripheral or side vision) may indicate a hole or tear. Other symptoms may include:

• cloudy, blurry, or wavy vision

• a dark shadow or curtain in your peripheral vision

How are they diagnosed?Your eye care provider dilates your eyes with eyedrops. Then he or she looks at your eyes through an ophthalmoscope (a lighted instrument for examining the inside of the eye) and a special lens.How are they treated?Your provider will seal the retinal holes and tears so that they do not get bigger, fluid does not get underneath the retina, and the retina does not detach. The main types of treatment are:

• Laser photocoagulation: Highly focused beams of light seal the tissue around the hole or tear and prevent fluid from entering the break. The procedure is generally quick and can be done in your health care provider’s office. Your eyes are dilated for this procedure. Your vision may be blurred for a few hours.

• Cryopexy: An instrument called a cryoprobe is used to freeze the tissue around the hole and secure it to the inside of the eyeball. You will be given local anesthesia. You can go home after the procedure. Your eye will be red for a few days after cryopexy. You may need to use eyedrops.

Rarely, retinal holes do not need treatment, but should be checked regularly.How long will the effects last?Treatments for retinal holes and tears are usually successful. However, the effect of the treatment is not immediate. That is, the holes do not seal immediately at the time of the treatment. Because of this delay in sealing, there is a small risk that the problem will progress to a retinal detachment before the holes have healed. There is also a chance that you will have a retinal hole or tear in another part of your eye later. Have your eyes examined regularly and tell all eye care providers that you have had retinal problems.How can I take care of myself?

• Follow your treatment plan.

• Have your eyes examined regularly and tell all eye care providers that you have had retinal problems.

How can I help prevent retinal holes and tears?Other than protecting your eyes from injury, there is no way to prevent retinal holes and tears. However, you can help prevent blindness if you see your eye care provider for regular checkups or as soon as you have symptoms of holes or tears.

RAJESH .DODDA

Congenital Glaucoma

 CLASSIFICATION

Congenital glaucomas are present at birth while infantile glaucomas refer to elevated ocular pressures and other sequelae with onset from birth up to three years of life. Developmental glaucomas are associated with developmental anomalies of the eye present at birth. Defective primary development of the outflow structures of the eye causes primary developmental glaucomas whereas other developmental ocular abnormalities secondarily affecting the aqueous outflow structures cause secondary developmental glaucomas (e.g. glaucoma secondary to persistent primary hyperplastic vitreous, spherophakia, retinopathy of prematurity, Sturge Weber syndrome, congenital ectropion uveae, etc). This review will focus on the most common form of developmental glaucomas seen in ophthalmic practice, Primary Congenital Glaucoma.The reader is referred to standard textbooks on glaucoma for a detailed description of the terminology and classification of developmental glaucomas. Buphthalmos is derived form the Greek term for ox-eye and refers to the significant enlargement of the eye that can occur as a consequence of any type of glaucoma present in infancy. Similarly, Hydrophthalmos in Greek refers to the high fluid content present with marked enlargement of the eye. These are merely descriptive terms with no implications on the etiology, pathogenesis or management of the eyes so affected, and are not used diagnostically in clinical practice.
Primary congenital glaucoma (commonly, alternately and widely referred to as primary infantile glaucoma as well) is described by Shaffer and Weiss¹ as follows:
Primary congenital glaucoma is the most common hereditary glaucoma of childhood, inherited as an autosomal recessive pattern, with specific angle anomaly consisting of absence of angle recess with iris insertion directly into trabecular surface. There are no other development anomalies of the eye. Elevated IOP results in corneal enlargement, clouding and breaks in Descemet's membrane.

Pathophysiology of Primary Congenital Glaucoma

IOP elevation in primary congenital glaucoma is due to an abnormal development of the anterior chamber angle that results in reduction of aqueous outflow facility and there is no uniform agreement among investigators on the nature of obstruction to aqueous flow in congenital glaucoma. Barkan² suggested incomplete resorption of mesodermal tissue led to formation of a membrane across the anterior chamber angle, referred to as the Barkan's membrane and forms the basis of the surgical procedure of goniotomy which results in cleaving of the membrane to increase aqueous flow. The existence of such a membrane has not been proved by light or electron microscopy. Maumenee³demonstrated abnormal anterior insertion of ciliary muscle over the scleral spur in eyes with infantile glaucoma. He observed that longitudinal and circular fibers of the ciliary muscles inserted directly onto the trabecular meshwork rather than the scleral spur and root of the iris inserts directly to trabecular meshwork. Anderson⁴ provided histopathological support for the high insertion of iris into trabecualr meshwork, suggesting this is due to a development arrest in the normal migration of anterior uvea across the meshwork in the third trimester of gestation. The eyes in primary congenital glaucoma are characterized by the appearance of the iris and ciliary body in the seventh of eighth month of gestation rather than the full term development of the infant. The iris and ciliary body have failed to recede posteriorly with resultant overlap of the iris insertion and anterior ciliary body over the posterior trabecular meshwork (Fig. 1). It has also been postulated that abnormal extracellular matrix and glycoproteins cause abnormal anterior segment development.
Primary congenital glaucoma appears to result from developmental anomaly of the anterior segment structures derived from the embryonic neural crest cells causing outflow obstruction to aqueous by several mechanisms. Developmental arrest may result in anterior insertion of iris, direct insertion of the ciliary body onto the trabecular meshwork and poor structural development of the scleral spur. The high insertion of the ciliary body and the iris onto posterior trabecualr meshwork may compress the trabecualr beams and the extracellular meshwork may be abnormal.

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R Krishnadas, R Ramakrishnan

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Epidemiology and Genetics

Primary congenital glaucoma is an extremely rare inherited eye disease and accounts for 0.01-0.04% of total blindness and is the most common form of glaucoma in children. The disease is usually manifested at birth or within three years of life. The incidence of primary

Fig. 1: Contrast the normal well-developed anterior chamber angle (above) as compared to the angle of the anterior chamber in an infant with primary congenital glaucoma (below). The features in the angle of congenital glaucoma include anterior insertion of iris, rudimentary scleral spur, insertion of ciliary muscle directly into the trabecular meshwork and undifferentiated trabecular meshwork. (Tripathi &Tripathi, Embryology of the anterior segment of the human eye)
congenital glaucoma in the west is estimated to be about one in 10-15,000 live births, but is likely to more common in the developing world like India, due to increased consanguinity among many ethnic groups in these populations. A population based assessment of childhood blindness in southern India has estimated the incidence to be about one in 3300 in the Indian state of Andhra Pradesh. While 60% children with congenital glaucoma present by 6 months of age, a majority (80%) are diagnosed by the first year of life. Males predominate in a ratio of 3:2, while the involvement is bilateral in about 70-80%. Most cases of primary congenital glaucoma are sporadic, while children with familial glaucoma reveal an autosomal recessive pattern with variable and incomplete penetrance. Autosomal dominant pattern of inheritance is also reported in some pedigrees. Genetic studies have revealed that mutations in the CYP1B1 gene encoding the cytochrome P450 enzyme in what is known as the GLC3A locus of the chromosome 2p21 are associated with primary congenital glaucoma⁵.
Recent studies have focused on the localization of this enzyme in this eye and its possible functions related to ocular development and possible molecular mechanisms by which the mutation can cause glaucoma. The generic defect is not totally penetrant which in other words means that there are people who do show the mutated gene type but do not have disease at birth or in infancy. This has suggested the possibility of a modifier gene which might modify the activity of CYP1B1. Recently a paper suggesting that a possible modifier may exist has been published. In the CYP1B1 knockout mouse it was observed that the phenotype was expressed only in tyrosinase deficient mice.¹¹
More recently Deepak Edward et al (personal communication) using immunohistochemistry have identified that CYP1B1 in fetal eyes and in adult eyes is mainly localized to the ciliary epithelium in the anterior segment and with very little expression in the trabecular meshwork. The expression in the ciliary epithelium appears to be confined to the non-pigmented ciliary epithelium. Based on this it has been hypothesized that CYP1B1 through an indirect mechanism or possibly through a chemical messenger affects the normal development of the trabecular meshwork leading to obstruction of aqueous humor outflow. This gene product is likely a substrate of the enzyme CYP1B1 and might be a protein product/cytokine present in the aqueous humor. Further studies are required, however, to substantiate the presence of these proteins in the aqueous humor of children with congenital glaucoma.
Ocular enlargement occurs due to the fact that the infant's eye is largely distensible since the corneal and scleral collagen are not mature enough to resist distention with increased IOP. The changes primarily affect the cornea, sclera, corneoscleral limbus, the optic nerve, scleral canal and the lamina cribrosa. Corneal enlargement is a very specific sign of congenital glaucoma. The normal neonatal horizontal corneal diameter at birth is 10-10.5 mm at birth and increases by about 0.5 to 1.0 mm in the first year of life. A horizontal corneal diameter of 12mm in the first year of life associated with corneal edema is pathognomonic of glaucoma (differential diagnosismegalocornea but the cornea is clear in this condition ). Asymmetrical enlargement of cornea is more easily diagnosed and is characteristic of congenital glaucoma. Corneal enlargement from elevated IOP is remarkable in the first three years of life though the sclera is deformable until about ten years of age (Figs 2 to 4).

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Congenital Glaucoma-A Brief Review

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Fig 2 : An infant with features typical of primary congenital glaucoma�Observe asymmetrical corneal enlargement and corneal edema

Fig 3 : Children with advanced congenital glaucoma. Observe buphthalmos with corneas exceeding 15 mm in diameter and corneal scarring. Children presenting with such late manifestations have poor visual prognosis to surgical or medical treatment. Early diagnosis and surgical correction of underlying pathophysiology is the key to success of treatment in these children

Fig. 4: Estimation of the horizontal corneal diameter is an essential tool in diagnosis of congenital glaucoma. A measurement exceeding 12 mm in a child is pathognomonic of glaucoma, provided other causes of megalocornea can be excluded

Clinical Features

History and Symptomatology
External Examiantion
Corneal diameter
Corneal edema
IOP elevation (tonometry)
Refractive error and amblyopia
Slit lamp evaluation and gonioscopy
Optic nerve examination

History and Symptomatology

Epiphora, photophobia and blepharospasm represent the classic triad of symptoms of congenital glaucoma. Any combination of these symptoms should arouse the suspicion of glaucoma in a child. These symptoms are a result of corneal irritation from corneal epithelial edema associated with elevated intraocular pressure (IOP). Infantile glaucomas may also present as a red eye mimicking conjunctivitis and resulting in a delay in diagnosis. Elevated IOP results in ocular enlargement with maximal enlargement occurring at the corneoscleral junction. Loss in corneal transparency with corneal haze may be initially intermittent and precede breaks in descemet membrane.

EXTERNAL EXAMINATION AND SLITLAMP BIOMICROSCOPY

Haab's striae⁶ are breaks in descemet membrane as increased IOP stretches the corneal endothelium and the Descemet's membrane and are characteristic of congenital glaucoma with onset before the age of three and in corneas with diameter exceeding 12.5 mm (Fig. 5). The edge of the rupture in descemet membrane contracts into ridges and scrolls, penetration of aqueous compounds any diffuse corneal edema.

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R Krishnadas, R Ramakrishnan

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Fig 5 : Haab�s striae typically seen in a child with megalocornea and primary congenital glaucoma.

Haab's striae result from new basement membrane laid down by the endothelial cells. These striae are horizontal and linear when seen centrally and curvilinear and vertical when they are peripheral and parallel the limbus. As IOP normalizes and corneal edema clears,endothelial overgrowth repairs the tears but linear striae persist. Reduced endothelial count in such eyes may be evident on specular microscopy. Persistence of elevated IOP in unresolved congenital glaucoma causes stromal corneal edema, corneal scarring and irregular corneal astigmatism.
Distention of sclera under the influence of elevated IOP causes scleral thinning with blue sclera with increased visibility of the underlying uvea, increased axial length and axial myopia and buphthalmos. Unilateral or asymmetric congenital glaucoma result in myopic astigmatism, anisometropia and amblyopia. Enlargement of the globe under the influence of IOP elevation in the first three years of life causes a myopic shift in the refractive status of the eye. Astigmatism is commonly owing to Haab's striae and amblyopia is the rule in asymmetricdal congenital glaucoma. Children between 3-10 years age with glaucoma develop progressive myopia under the influence of elevated IOP due to scleral distension and stretching although they exhibit no corneal enlargement. Loss of hyperopia in aphakic children is evidence of glaucoma in aphakia.

IOP and Tonometry

The most accurate measurements of IOP are those obtained in an awake and cooperative child under topical anesthesia and blepharospasm or a struggling/crying child can artifactually elevate IOP. Sedatives and anesthetics alter IOP to a varying extent. While most inhalational anesthetics like halothane lower IOP, succinylcholine and ketamine elevate IOP. Most reliable IOP are obtained under intramuscular ketamine and in the lighter planes of inhalational anesthetics prior to intubation. Perkins tonometer and tonopen are reliably used to measure IOP in children. Infants and \\young children appear to have IOP lower than those expected in adults: Mean IOP of 9.59 mmHg was found in the newborn which had risen to 13.95 by 7 or 8 years of age. Infants with primary congenital glaucoma usually present with IOP exceeding 30-40 mmHg when unanesthetised, but may be much lower under the influence of inhalational anesthetics.

Gonioscopic Evaluation of the Anterior Chamber Angle in Primary Congenital Glaucoma

Evaluation of the anterior chamber angle aids in diagnosis of primary congenital glaucoma and helps in differentiating this condition from other entities with similar clinical features. Ideally a Koeppe's gonio lens with a portable slit lamp delivery system is utilized for the purpose. A Goldmann gonio lens is also used for viewing the angle through the operating microscope. Corneal clouding may obscure the details of the angle which may be improved by using topical glycerine or 70% alcohol with a cotton applicator. Edematous epithelium may also be removed using a surgical blade to improve visualization of the angle and the anterior chamber.
The anterior chamber angle in infants vastly differs from that of adults. In the normal eye of the newborn, the iris usually inserts posterior to the scleral spur. The iris insertion into the angle is flat and the angle recess is not formed. The trabecular meshwork appears thicker and more translucent than that of an adult. Pigmentation is absent unlike in adults. Gonioscopy of the eyes in infants with primary congenital glaucoma reveals anterior insertion of the iris directly into the trabecular meshwork. The surface of the trabecular meshwork has a stippled appearance and the meshwork appears thicker than normal. The peripheral iris shows thinning of the anterior stroma. The angle is usually devoid of vessels, although loops of vessels from the major arterial circle is seen above the iris surface and has been referred to as the Loch Ness Monster phenomenon. The peripheral iris inserting into the trabecular meshwork may appear translucent and is often referred to as the Lister's morning mist.

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Congenital Glaucoma-A Brief Review

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Optic Nerve Changes in Congenital Glaucoma

Optic nerve cupping occurs rapidly in infants with elevated IOP and unlike in adult eyes is also rapidly reversible with normalization of IOP⁷. Reversibility of optic nerve cupping with treatment in congenital glaucoma appears to be due to incomplete development of the connective tissue comprising the lamina cribrosa with posterior movement of the lamina and enlargement of the scleral canal and consequently of the cup to disc ratio in response to IOP elevation, and the more resilient connective tissue in the optic nerve head cause reversal of cupping with normalized IOP. Persistent IOP elevation, however, causes glaucomatous optic atrophy due to loss of ganglion cells.
Uncontrolled and refractory IOP elevation in congenital glaucoma causes corneal scarring and ulceration and perforation with continued enlargement of the cornea and the globe. Stretching and rupture of zonules causes lens subluxation; hyphema, retinal detachment and pthisis bulbi are often the final outcome of untreated or refractory glaucomas in infancy and childhood.
Ultrasonic ocular biometry aids in diagnosis and follow up of children with congenital glaucoma. Ultrasonic measurements of the axial length of the eye is a valuable tool to diagnose congenital glaucomas. The anterior chamber depth and axial length are significantly increased while the thickness of the lens is decreased. The reduction in lens thickness and corneal flattening limits the myopic shift seen with increasing axial length of the eye with progressive glaucoma.

Differential Diagnosis of Primary Congenital Glaucoma

Although a child with corneal and ocular enlargement and corneal haze due to edema presenting with blepharospasm, photophobia and tearing typically has primary congenital glaucoma, it is essential to exclude other childhood eye diseases with overlapping signs and symptoms simulating congential glaucoma.
Nasolcacrimal duct obstruction in the newborn and infants is associated with tearing, although photophobia and other corneal changes typical of congenital glaucoma is absent. Obstruction of nasolacrimal passage is also associated with fullness in the region of the lacrimal sac and a chronic mucopurulent discharge. Redness and tearing can be a manisfestation of any of the several causes of conjunctivitis in children, including bacterial, viral and chlamydial, including the chemical conjunctivitis as a result of silver nitrate prophylaxis. Corneal epithelial defects and abrasions are frequent causes of acute ocular irritation, tearing and photophobia.
Corneal dystrophies (Meesman's and Reis Bucklers) which present in the early years of life may also manisfest with ocular irritation and tearing and need to be differentiated from congenital glaucoma. Congenital hereditary endothelial and stromal dystrophy also manifest with corneal edema, and tearing differentiated due to absence of corneal enlargement. Inflammatory keratitis and iridocyclitis occasionally cause corneal clouding and edema associated with pain and tearing. Rubella keratitis typically causes corneal clouding and enlargement even in the absence of secondary glaucoma and is difficult to be differentiated from congenital glaucoma. The fact that secondary glaucoma due to abnormal anterior chamber development commonly accompanies Congenital Rubella Syndrome further compounds the problem of accurate diagnosis and appropriate treatment. Characteristically, when rubella viremia is present in the third trimester of pregnancy, anomalous anterior chamber angle development results in glaucoma with no other features of the maternal rubella syndrome.
Extreme degrees of axial myopia can present with enlarged globes and large corneas, but features of posterior pole such as tilted optic discs, peripapillary myopic crescent and choroidal mottling which are not characteristic of congenital glaucoma serve to distinguish the two conditions. Megalocornea is a condition characterized by large corneas, often upto 14-16 mm in diameter. Features of congenital glaucoma, such as corneal edema and descemet membrane breaks, elevated IOP and optic nerve cupping are absent. The condition appears to have sex linked inheritance with 90% reported in males and families have been studied in which some members have megalocornea and others, primary congenital glaucoma. Some investigators consider megalocornea to be a forme fruste of primary congenital glaucoma, and hence individuals with large corneas need to be followed up for life to exclude glaucoma.
In sclerocornea, the opaque corneal tissue extends onto the cornea. Obstetric trauma can cause rupture of the descemet membrane with resultant corneal edema and clouding. The breaks in birth trauma are usually oriented vertically, although exceptions do occur with the breaks being distributed in a horizontal or curvilinear fashion. Birth trauma is unilateral, with no corneal enlargement or elevated IOP and associated with periorbital skin changes like bruising when examined immediately after birth. The left eye is more often involved since the left anterior occiput is the most common presentation of the infant's head.
Several inborn errors of metabolism cause corneal clouding and mimic congenital glaucoma. Mucopolysaccharidoses are characterized by excessive storage of mucopolysaccharides due to their defective degradation from lack of the lysosomal acid hydrolases- examples include Hurler's Syndrome, Scheie Syndrome, Morquio Syndrome and the Maroteaux-Lamy Syndrome. Cystinosis is due to defective lysosomal

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R Krishnadas, R Ramakrishnan

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transport system with deposition of cystine crystals in cornea presenting with intense photophobia; with renal failure and salt-pepper retinopathy in the nephropathic type cystinosis. Mucolipidosis, sphingolipidoses, metachromatic leucodystrophy, glucose 6 phosphate deficiency are other storage diseases associated with corneal clouding, but differentiated from congenital glaucoma by absence of elevation of IOP and corneal enlargement.
Congenital Hereditary Endothelial Dystrophy (CHED) is an important condition that is mistaken for congenital glaucoma, since the condition is manifest at birth or within first two years of life. It is inherited both as autosomal recessive and dominant condition with variable expressivity with mild posterior corneal changes to diffuse corneal edema. The cornea is thickened to three times normal, often over-estimating the IOP measured by applanation tonometry, but corneal enlargement is typically absent. Corneal clouding is often symmetrical with no descemet breaks or corneal scarring. Although some authors report tearing and photophobia in children with CHED, this is extremely uncommon in the authors' clinical experience and the absence of tearing, photophobia, blepharospasm associated with absence of corneal enlargement is considered typical of CHED and helps differentiate from congenital glaucoma. The distinction, nevertheless is crucial, since a diagnosis of congenital glaucoma necessitates immediate surgical intervention to preserve visual function. In the instance of difficulty in differential diagnosis, especially in the first few years of life, it is prudent to periodically evaluate these children, especially to exclude corneal or ocular enlargement ( by ultrasonography to exclude axial myopia). It is, however, not unusual to encounter congenital glaucoma associated with CHED and in these eyes, corneal edema persist after normalization of IOP following surgical intervention. The precise diagnosis, however, is established only after the histopathological examination of the corneal buttons obtained after penetrating keratoplasty in these eyes.

Management

Early detection and appropriate treatment of primary congenital glaucoma cannot be overemphasised, since neglect and inappropriate treatment can cause profound visual loss in the children with increase in the blind-years. With improvement in the understanding of genetics and pathophysiology of the disease and improvised surgical techniques, it is often possible to prevent the children going blind, with preservation of useful vision. The principal aim in the management of children with congenital glaucoma is preservation of visual function, ocular structural integrity, promotion of development of binocular stereoscopic vision and early visual rehabilitation to prevent amblyopia.
Primary congenital glaucoma is an essentially surgical disease and medical treatment is used only as a temporizing measure or as a supplement to surgical intervention when IOP remains difficult to be controlled. Lasers also have only a supportive role. Several factors, including the structural defects characterizing glaucoma, age at presentation, corneal clarity and enlargement, associated systemic features and severity of glaucoma influence the ophthalmologists' decision on the type of treatment necessitated. It is important to discuss the prognosis with the parents and ensure they remain committed to the child's prolonged treatment.

MEDICAL THERAPY FOR PRIMARY CONGENITAL GLAUCOMA

Since primary congenital glaucoma is essentially characterized by elevation of IOP due to a structural defect, medical therapy plays little role in primary therapy of glaucoma and the treatment is essentially surgical to overcome the developmental defect causing resistance to aqueous outflow. However, drugs to reduce IOP may be used to supplement surgical treatment when intraocular pressure reduction is considered inadequate or when surgery fails to adequately contain the pressure elevation. There are no randomized controlled clinical trials available on the efficacy of pressure lowering drugs in children and the available data of safety and efficacy are from studies conducted in adults and these drugs need to be used in children with caution, especially in those with systemic diseases; and carefully evaluate the risk and benefits of individual therapeutic agents and use the minimal effective dose of the drugs possible to achieve the maximal pressure lowering effect, while monitoring the children for ocular and systemic side effects.
ß Blockers: Timolol is the most widely used beta blocker in reduction of intraocular pressure in children, but various studies that have evaluated timolol either as a single or adjunctive drug have reported adequate IOP reduction in only a third. Plasma timolol levels in children, particularly in infants, after treatment with 0.25% timolol significantly exceed that seen in adults after instillation of 0.5% timolol. Increased concentration of plasma timolol in children explained by the smaller volume of distribution of the drug as compared to adults and hence an increased likelihood of systemic adverse effects in the young. Reduction in heart rate, exacerbation of asthma and apnoea have been reported, necessitating withdrawal of the drug due to adverse effects in 4-13% of children treated. A detailed systemic evaluation to exclude pulmonary and cardiac diseases is to be performed prior to administration of this drug in children and infants and needs to be avoided in neonates and the premature due to risk of sleep apnoea. When indicated, timolol gel forming solutions may be preferred, since this formulation is expected to reduce the adverse effects of the active drug due to lesser systemic absorption.
Carbonic Anhydrase Inhibitors: Systemic CAI, such as acetazolamide have been recommended in the dosage of 5-10 mg/kg/day in divided doses as a temporizing measure to reduce IOP and corneal edema prior to surgery. Prolonged treatment with acetazolamide is associated with growth suppression and metabolic acidosis in children. They are also subject to other serious adverse effects like drug idiosyncracy and

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Congenital Glaucoma-A Brief Review

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bone marrow suppression and prolonged therapy with oral acetazolamide is best avoided. Topical CAI, as 2% dorzolamide, effectively reduces IOP in children, though the IOP lowering potency is studied to be lowered as compared to oral acetazolamide. Topical dorzolamide is currently the preferred IOP lowering agent of choice in infants and children and may administered two or three times daily, since the drug is devoid of serious systemic adverse effects of timolol and oral acetazolamide. In older children with no contraindications, fixed combination therapy of timolol and dorzolamide may be used, which is convenient and gives the advantage of use of employing two drugs while simplifying the dosage schedule.
Prostaglandin Analogues: The use of prostaglandins and their efficacy in children with congenital glaucoma is not adequately studied. Even in older children with Struge Weber suyndrome, only a third of patients treated with latanoprost responded favorably with therapy. Use of latanoprost or any of the prostaglandin analogues in childhood glaucomas is currently not recommended.
Alpha Receptor Agonists are an important adjunct in treatment of adult glaucomas. Specific Alpha² receptor agonists like brimonidine is widely used in management of chronic glaucomas. However, brimonidine easily crosses the immature blood brain barrier of children and causes adverse central nervous system effects like drowsiness and even respiratory depression. Apart from extreme fatigue, infants on brimonidine have developed recurrent episodes of unresponsiveness, hypotension, hypotonia, hypothermia and bradycardia. Failure of recovery from anesthesia and death of premature infants have been attributed to use of brimonidine. Use of brimonidine and other alpha receptor agonists are not recommended in children younger than eighteen years.
Cholinergic drugs ( Pilocarpine) do not seem to have a useful role in medical treatment of congenital glaucoma. Although miotics increase facility of outflow facility and reduce IOP in normal and open angles, they do not seem to be effective in eyes with congenital glaucoma with an abnormally developed angle with anterior insertion of the ciliary musculature into the trabecular meshwork. Pilocarpine, may however, be useful in children with glaucoma in aphakia and pseudophakia with open iridocorneal angles.

SURGICAL TREATMENT OF PRIMARY CONGENITAL GLAUCOMA

Early detection and surgical treatment is of prime importance in ensuring IOP reduction and visual preservation in children with congenital glaucoma. In eyes with early congenital glaucoma with corneal edema and minimal ocular and corneal enlargement, goniotomy is the initial procedure of choice. However, in India and other developing nations most children with congenital glaucoma report with corneal enlargement and scarring and goniotomy is usually difficult owing to poor visualization of the angle structures and need ab externo trabeculotomy, often combined with trabeculectomy.

Goniotomy

Goniotomy is considered as the treatment of choice by many surgeons in primary congenital glaucoma, provided the cornea allows satisfactory visualization of angle. The procedure, initially practiced by Barkan⁸, aims to remove the obstructing tissue in the angle that causes resistance to aqueous flow (Fig. 6).

Fig 6 : The goniotomy procedure in progress

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R Krishnadas, R Ramakrishnan

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Procedure

Corneal edema may be cleared by the use of 20% glycerol drops immediately before surgery; if unsuccessful, epithelial debridement with absolute alcohol provides adequate view of the angle to allow goniotomy in most of the cases.

• To be performed safely - general anesthesia, on operating microscope, a contact lens (e.g. Barkam lens) and a tapered goniotomy blade are required.
• Preoperatively pilocarpine helps to open the angle and protects the lens by constricting the pupil.
• The inner portion of the nasal trabecular meshwork over 90-120 degree is incised with the goniotomy bade under direct visualization of the angle with the help of gonio lens.
• A mild hyphema on withdrawal of the knife from the anterior chamber is typical and indicates a correctly placed incision.
• Goniotomy can be repeated in the event of unsuccessful IOP control preferably in the temporal quadrant.
• Goniotomy presumably relieves the compressive traction of anterior uvea on the meshwork and eliminates any resistance imposed by incompletely developed inner meshwork.
• Advantages of Goniotomy: Less traumatic and safe in experienced hands, rapid, can be repeated and spares the conjunctiva for possible later surgery.
• Disadvantages: Procedure not possible if details of angle structure are not clear, technically demanding requires special instruments, needs experienced surgeons and possibility of corneal endothelial, angle and lens trauma.
• Success rate following multiple goniotonies in 70-90% with medium term follow up.
• Moor fields experience showed a 20% relapse rate over a 30 years-period with no peak age of relapse emphasizing the importance of life-long follow-up.
• Infants presenting between 2 to 8 months have best prognosis and surgery becomes less effective with increasing age. The worst prognosis occurs for infants with elevated pressures and cloudy corneas at birth.

TRABECULOTOMY⁹

It is the procedure of choice by many surgeons particularly when cornea is opaque. Corneal clarity is not a pre- requisite since the procedure is ab externo and identifies the schlemm's canal by external approach. Results of trabeculotomy in several studies have reported to be as favorable as initial goniotomy procedures.

Procedure

A limbal or fornix based conjunctival flap is dissected. A trabeculectomy scleral flap is fashioned and Schlemm's canal located by slowly deepening a 2 mm radial incision placed at the corneal scleral junction. An accurate knowledge of the surgical anatomy of the limbus is essential to identify the Schlemm's canal. The junction of the blue white sclera marks the location of the scleral spur and the Schlemm's canal is a mm anterior to this structure.The trabeculotome is gently threaded into the canal and swept into the anterior chamber, rupturing the internal wall of Schlemm's canal and trabecular meshwork and directly exposing it to aqueous humor. The procedure is repeated to other side of the canal. The scleral flap is tightly closed. Accurate localization of Schlemm's canal is the most important step. Schlemm's canal is not found in 4-20% of the cases. A mild to moderate hyphema is a regular occurrence, and often confirms accurate identification of the Schlemm's canal. Appearance of aqueous as the lumen of the canal is opened is also evidence of entry into the canal of Sclemm.
Mendincino et al have described a 360-degree suture trabeculotomy using 6/0 polypropylene which is threaded into entire Schlemm's canal from 1 or 2 cut down sites and when the suture is pulled towards the entry of the canal in the surgical limbus, the entire lumen of the canal is opened into the anterior chamber.

Advantages

The procedure can be performed in opaque corneas, many components of technique similar to trabeculectomyand higher success rate has been reported by some studies when trabeculotomy is combined with Trabeculectomy. Even if one fails to accurately identify the Schlemm's canal, the procedure could be completed by proceeding with trabeculectomy as in adult glaucomas.

Disadvantages

Angle structures are not directly visualized in trabeculotomy hence complications though seldom serious may be more frequent than goniotomy. Potential complications include descemets membrane stripping, iris prolopse, iridodialysis, cyclodialysis with persistent hypotony, false passages, lens subluxation and a prolonged flat anterior chamber. It also damages conjunctiva and prejudices success of future filtering surgery.
Primary trabeculectomy is also an optional surgical procedure in eyes with congenital glaucoma and most ophthalmologists are familiar with the technique. The procedure is also easier to perform than goniotomy or trabeculotomy. Several published reports have documented comparable results with primnary trabeculectomy as compared to goniotomy or trabeculotomy. In addition, a combined trabeculotomy and trabeculectomy may be performed as a primary or secondary procedure

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Congenital Glaucoma-A Brief Review

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in eyes that are likely to have poorer surgical outcome following trabeculotomy or goniotomy owing to advanced nature of the disease. A higher incidence of successful intraocular pressure control with primary combined trabeculotomy and trabeculectomy has been reported in some ethnic groups, especially in the developing world like India,¹⁰ where children present late with advanced disease and buphthalmos (Fig. 7). In eyes with refractory congenital glaucoma, trabeculectomy with antimetabolites, glaucoma drainage devices and laser cyclodestructive procedures are attempted.

Fig 7 : A child with adequate IOP control following combined trabeculotomy with trabeculectomy. Asymmetric corneal enlargement and corneal scarring inferior to the visual axis in the right eye can still be seen. Such children often have productive vision with visual rehabilitation and treatment for amblyopia, which is an essential component of integral treatment of congenital glaucoma