Chapter 132 – Coexistent Optic Nerve and Macular Abnormalities
GARY C. BROWN
MELISSA M. BROWN
• A heterogeneous group of optic nerve disorders that have secondary pathological effects on the macular retina.
• Structural changes of the optic nerve.
• Secondary retinal detachment, retinoschisis, or macular edema.
• Optic nerve pit.
• Morning glory optic disc anomaly.
• Optic nerve coloboma.
• Optic nerve edema.
• Choroidal neovascularization.
• Optic nerve abnormalities may be associated with macular abnormalities, the most common being detachment of the macular retina. Choroidal neovascularization, macular edema, retinoschisis, and lipid exudation also may be found.
CONGENITAL PIT OF THE OPTIC DISC
Congenital pits of the optic disc are localized excavations that typically measure less than one half a disc diameter in width. Although over 50% are located on the temporal aspect of the optic disc ( Fig. 132-1 ), they can be located anywhere on the nerve head. Approximately one third are located centrally ( Fig. 132-2 ). Those located centrally on the optic disc are not associated with retinal detachment.
EPIDEMIOLOGY AND PATHOGENESIS
Optic pits are believed to be secondary to a disturbance in the development of the primitive epithelial papilla, but the exact cause is uncertain. In some instances they can be associated with classic retinochoroidal colobomas, as well. In these instances it is possible that they are secondary to a defect in closure of the embryonic fissure.
Kranenburg found pits in approximately 1 per 11,000 patients. Because approximately 40% of pits are or have been associated with retinal detachment (see Fig. 132-1 ), about 1 per 25,000 examined patients demonstrate an optic pit with evidence of a previous or present serous detachment of the neural retina. Pits are unilateral in 95% of cases, and in 85% of unilateral instances the optic disc on the side of the pit is larger than the contralateral optic disc. Occasionally, more than one pit can be seen on a single optic disc.
Figure 132-1 Temporally located congenital optic pit associated with a localized retinal detachment in the macula in the eye of a 15-year-old girl. Peripapillary retinal pigment epithelial changes are seen adjacent to the pit. The visual acuity was 20/60 (6/18).
Figure 132-2 Centrally located congenital pit of the optic disc.
The pits vary in color. Approximately 60% are gray, 30% are yellow, and 10% are black. The depth is variable and usually ranges from less than a diopter to several diopters. Peripapillary retinal pigment epithelial changes or choroidal atrophy or both are seen in 95% of eccentrically located pits (see Fig. 132-1 ). It is believed that this peripapillary disturbance may predispose to peripapillary choroidal neovascularization in rare instances ( Fig. 132-3 ).
Figure 132-3 Peripapillary choroidal neovascularization adjacent to a congenital pit of the optic nerve head located at the 9:30 position. (Courtesy of Dr. W. Jackson.)
Optic pits often are associated with visual field defects. If the enlarged blind spots (because of the large optic disc) seen in 85% of cases are excluded, as well as the defects that occur secondary to retinal detachment in another 40%, about 60% of eyes that have optic pits have defects that result from the pits. These can mimic exactly those seen with glaucoma and include nasal and temporal steps, altitudinal defects, paracentral scotomas, arcuate scotomas, generalized constriction, and localized constriction. Centrally located pits, as well as eccentrically located pits, may be associated with field defects.
Although an associated maculopathy was noted first by Reis in 1908, it was not until 1958 that Petersen emphasized the relationship between congenital optic pits and a central serous chorioretinopathy–like picture.
The cause of the subretinal fluid remains debatable. The most likely sources are fluid from the vitreous cavity  or from the subarachnoid space.  Leakage from the choroid, from vessels at the base of the optic pit, and through macular holes also have been suggested, although these probably are less likely sources of the subretinal fluid. Experimental evidence from collie dogs shows a connection among the vitreous cavity, the pit, and the subretinal space in eyes that have congenital nerve head pits and retinal detachment ( Fig. 132-4 ). In addition, active transport of India ink from the vitreous cavity into the pit and subretinal space has been shown. Convincing similar histopathology has not been demonstrated in humans. Nevertheless, in most human eyes that have associated retinal detachment, a small fenestration can be seen in the membrane that often overlies congenital optic pits. It is thought that intravitreal traction on the optic pit by an anomalous Cloquet’s canal may play a role in the development of macular detachment.
The retinal detachments usually extend into the macular region or slightly beyond. They typically are shallow, only rarely are bullous, and may be associated with subretinic precipitates that occur secondary to macrophages that have imbibed retinal pigment epithelial cells and deposited on the undersurface of the retina. Cystic changes are seen frequently in the foveal region of the detached retina, and apparent macular holes develop in about 25% of eyes that have macular retinal detachment. The macular holes seen with optic pits differ from idiopathic macular holes in that the former often appear to have an intact, overlying internal limiting membrane. If a macular hole develops, the prognosis for visual return to better than 20/200 with treatment is poor. Macular holes can develop within 2 weeks of the onset of retinal detachment.
A splitting of the retinal layers occurs in many eyes that have optic pit and macular retinal detachment. This was noted first by
Figure 132-4 Histopathology of a collie dog eye with a congenital optic pit and associated serous retinal detachment. Vitreous gel has entered the pit from the vitreous cavity, and a connection exists between the pit and the subretinal space (periodic acid–Schiff).
Lincoff et al. and has been referred to as a retinoschisis, although it is unrelated to either the typical juvenile or senile retinoschisis. The area of schisis tends to be larger than the area of subretinal fluid.
The mean age at the time of onset of retinal detachment is about 30 years, although it can occur as early as the first decade of life or as late as the ninth decade. Larger pits and temporal location appear to be predisposing factors to the development of retinal detachment.
Systemic associations typically are not seen in conjunction with congenital optic pits. Nevertheless, an association with basal encephalocele has been described.
TREATMENT, COURSE, AND OUTCOME
Retinal detachments associated with optic pits may fluctuate and occasionally resolve without therapy. The natural course of untreated macular retinal detachment, however, is poor. The Wills eye series showed that among untreated eyes that had an optic pit and macular retinal detachment, 55% had a visual acuity of 20/100 (6/30) or less after at least 1 year of follow-up. Data from a more recent series from Iowa showed that 80% of such affected eyes eventually dropped to a visual acuity of 20/200 (6/60) or worse. Although there have been no clinical trials to study the effect of treatment, a somewhat comparable 44% of laser-treated eyes have vision less than 20/100 (6/30) after 1 year. Furthermore, among laser-treated eyes, only 16% have subretinal fluid at the end of 1 year, versus 75% of those that have not undergone photocoagulation. 
It is agreed generally that peripapillary laser therapy should be considered for cases of congenital optic pit associated with macular retinal detachment. The most widely used technique is to place two to three rows of 200?µm spot-size burns in a peripapillary distribution temporally ( Fig. 132-5 ). The treatment is extended into flat retina, both superiorly and inferiorly to the subretinal fluid, to allow the retina to adhere to the retinal pigment
Figure 132-5 Two rows of 200?µm spot-size laser burns applied to the peripapillary fundus in an eye with a congenital optic pit and macular retinal detachment. The treatment is carried into flat retina superiorly and inferiorly to the area of detachment, so the retinal pigment epithelium can adhere to the retina and, hopefully, to continue that adherence centrally.
epithelium (RPE), starting at the edges of the area of detachment. It is undesirable to produce burns that traverse the full thickness of the retina, especially in areas of flat retina, because these may create arcuate scotomas because of the close proximity to the optic disc.
The subretinal fluid resolves in 50% of cases after laser therapy, typically within several weeks ( Fig. 132-6 ).  If the treatment is ineffective, it can be repeated several months later. The greater the separation of the peripapillary retina from the underlying RPE, the less the chance of the treatment being successful.
If laser therapy does not flatten the retina after a second application, the possibility of additional laser treatment in combination with a pars plana vitrectomy and air–gas fluid exchange can be considered.  Because the retinal detachment generally is shallow, internal drainage of subretinal fluid usually is not necessary. It may actually be undesirable, because the vitreous gel can be very difficult to separate from the retina in young people. An inability to separate the gel may result in later retinal detachment as the remaining vitreous contracts.
Vitrectomy flattens the retina in an additional 80% of eyes that do not respond to laser therapy. Thus, the subretinal fluid can be eradicated with some form of treatment in at least 90% of eyes that have a macular retinal detachment (50% initially with laser, and 80% of the remaining 50% of recalcitrant cases with subsequent vitrectomy). The subretinal fluid initially may be displaced peripherally to the macular region with vitrectomy and require several weeks or longer to resolve after the intravitreal gas has dissipated. Laser therapy in combination with a perfluoropropane (C3 F8 ) gas injection into the vitreous cavity without concurrent vitrectomy (pneumatic retinopexy) also has been successful in ultimately flattening the retina in approximately 90% of eyes that have a macular detachment.
Subretinal fluid present in the macula for several months does not preclude good visual return if the retina is flattened and a macular hole has not developed. Subretinic precipitates typically resolve once the detached macular retina is flattened.
OPTIC NERVE COLOBOMA
Colobomas of the eye can arise anywhere along the line of fusion of the embryonic fissure, which extends from the optic disc posteriorly to the inferior pupillary frill of the iris anteriorly. The fissure begins to close centrally at 5–6 weeks of gestation. Failure of closure of the superior end produces an optic nerve
Figure 132-6 The same eye as shown in Figure 132-1 almost 3 years after laser therapy. The subretinal fluid is gone and the visual acuity is 20/25 (6/8).
Figure 132-7 Equator-plus photograph of a retinochoroidal coloboma. The embryonic fissure has closed partially, as shown by the normal rim of peripheral fundus inferiorly.
coloboma, whereas more widespread failure to close causes a retinochoroidal coloboma ( Fig. 132-7 ), sometimes in combination with an iris coloboma. In eyes with iris and retinochoroidal colobomas, it is not uncommon to see a normal fundus appearance anteriorly where the embryonic fissure started to close.
Both retinochoroidal and optic nerve colobomas may be associated with systemic abnormalities. Included among these are abnormalities of the central nervous, cardiovascular, genitourinary, musculoskeletal, gastrointestinal, and nasopharyngeal systems. One syndrome found in conjunction with retinochoroidal colobomas that has received particular attention is the CHARGE syndrome (coloboma, heart disease, atresia choanae, retarded growth, genital hypoplasia, ear anomalies, with or without deafness).  Renal hypoplasia also has been associated with optic nerve coloboma, retinochoroidal coloboma, congenital optic pit, and the morning glory optic disc anomaly. This has been referred to as the renal coloboma syndrome.  A mutation of the PAX2 gene has been noted in 50% of such cases.
Among the ocular abnormalities associated with both optic nerve and retinochoroidal coloboma is retinal detachment. Retinochoroidal colobomas also have been associated with choroidal neovascularization of the macula that originates at the edge of the colobomatous defect.
Figure 132-8 Rhegmatogenous detachment in an eye with a retinochoroidal coloboma. A peripheral retinal break was noted and the detachment was repaired successfully using a scleral buckling procedure.
The retinal detachments associated with retinochoroidal colobomas can be rhegmatogenous ( Fig. 132-8 ) or non-rhegmatogenous. If the retinal break is located peripherally, scleral buckling surgery may be effective.
If the break is located within the detached intercalary membrane (dysplastic retina) overlying the colobomatous defect, laser treatment can be given to the normal retina surrounding the coloboma in conjunction with a pars plana vitrectomy and an air–gas fluid exchange. In essence, the colobomatous defect should be treated as if there is a retinal break in any area of detachment that involves it. In some instances, the Schliering phenomenon can be seen during drainage via suction with an extrusion cannula, when a difficult-to-see break occurs within the intercalary membrane. In some instances, silicone oil tamponade with vitrectomy has been advocated. There is some controversy about the use of silicone oil in eyes with excavated defects of the optic nerve, because it is uncertain whether there is a communication between colobomatous optic nerve defects and cerebrospinal fluid in some eyes. Little is known about possible adverse effects of silicone oil if it gains access to the subarachnoid space.
The success rate for repair of retinal detachment associated with retinochoroidal colobomas was poor prior to the advent of vitrectomy. Using buckling and vitrectomy techniques, the retina remains flattened after 1 year in about 81% of cases, with approximately 70% of all eyes recovering vision to 20/400 or better. It should be noted, however, that the vision in eyes with optic nerve or retinochoroidal colobomas may be poor even without retinal detachment.
Retinal detachments associated with solely optic nerve colobomas typically are nonrhegmatogenous ( Fig. 132-9 ). Overall, the entity is less well described in the literature than detachment associated with optic pits.  The origin of the subretinal fluid in this colobomatous variant is unclear. These detachments are treated in a manner similar to retinal detachments associated with congenital optic pits. If the subretinal fluid seen in conjunction with an optic nerve coloboma is minimal and borders only a portion of the optic disc, laser therapy alone to the peripapillary area of retinal elevation and adjacent flat retina can be considered. Unfortunately, these detachments often are more pronounced than those associated with optic pits and, therefore, cause more severe visual loss. If the detachment is bullous, it is usually necessary to perform a pars plana vitrectomy, with internal drainage of subretinal fluid and laser therapy to the peripapillary region of the detached retina. If the subretinal fluid completely surrounds the optic disc, 360-degree laser therapy
Figure 132-9 Optic nerve coloboma associated with a bullous retinal detachment. After multiple vitrectomies, including one that employed the injection of intravitreal silicone oil, the retina eventually was flattened with an air–gas fluid exchange.
Figure 132-10 Morning glory optic disc in this left eye is associated with a shallow retinal detachment. The yellow pigment that overlies the area of subretinal fibrosis at the 3 o’clock position is due to the xanthophyll pigment in the fovea, which is abnormally close to the disc.
should be given lightly to minimize the chance of damaging the short posterior arteries that supply the prelaminar portion of the optic nerve head.
MORNING GLORY OPTIC DISC ANOMALY
The morning glory optic disc    is characterized ophthalmoscopically by:
• An enlarged disc with central excavation
• A central tuft of dysplastic white retina
• Peripapillary subretinal fibrosis
• Straightened retinal vessels that often are sheathed and emanate from the edge of the disc ( Fig. 132-10 )
The entity is most commonly unilateral but also can be bilateral. As is the case with both congenital pit of the optic disc and optic nerve coloboma, basal encephalocele has been described in association with the morning glory disc anomaly.
Approximately one third of reported cases of the morning glory disc anomaly have been associated with nonrhegmatogenous retinal detachment that is connected to the optic disc. Retinal detachment can occur later but most typically occurs
during the first and second decades of life. The origin of the subretinal fluid is unclear.
The detachments can be shallow (see Fig. 132-10 ) or bullous. Peripapillary laser therapy alone can be considered for shallow, localized retinal detachment, but with bullous retinal detachment, pars plana vitrectomy in combination with peripapillary laser therapy and internal drainage of subretinal fluid may be necessary to flatten the retina. Therapy for bullous detachments, especially in children, may not be successful. Optic nerve sheath decompression also has been reported to treat this form of retinal detachment, but its exact role is uncertain.
OTHER OPTIC NERVE ABNORMALITIES ASSOCIATED WITH MACULAR PATHOLOGY
ABNORMALITIES ASSOCIATED WITH CHOROIDAL NEOVASCULARIZATION
A number of optic nerve abnormalities have been associated with peripapillary choroidal neovascularization. Among these are drusen of the optic disc ( Fig. 132-11 ), papilledema, papillitis associated with multifocal choroiditis, and congenital pits of the optic nerve head. It is believed that these abnormalities, in some way, disrupt the peripapillary Bruch’s membrane, which predisposes to the development of new vessel growth.
Laser therapy is often of benefit in the eradication of peripapillary choroidal neovascularization. When the membrane extends to within 2500?µm from the center of the foveola, it often falls into the extrafoveal group studied in the Macular Photocoagulation Study. In this instance, laser photocoagulation has been shown statistically to be of benefit. If the membrane has not grown into the subfoveal region, the visual prognosis with laser therapy is reasonable. The authors usually treat temporally located, peripapillary choroidal neovascularization even if it has not extended to within 2500?µm from the center of the foveola. The morbidity associated with such treatment is low, although the morbidity associated with choroidal neovascular membranes that eventually reach the central macula is high.
ABNORMALITIES ASSOCIATED WITH EXUDATION
Abnormalities that cause papillitis can lead to severe chronic leakage of plasma and lipid products that extends into the central macula. The lipid is located within the outer plexiform layer (Henle’s fiber layer) and often has the configuration of a hemi-macular star or a full macular star. When this hard exudate is present, retinal thickening (macular edema) often is seen concomitantly.
Among the specific entities that can cause papillitis and subsequent hard exudation into the macula are idiopathic optic neuritis, radiation optic neuropathy ( Fig. 132-12 ), malignant hypertension, and anterior ischemic optic neuropathy. An idiopathic form of anterior optic neuropathy with stellate exudate is referred to as Leber’s stellate optic neuropathy. It is likely that almost any cause of acute optic neuropathy can produce the clinical picture of optic disc edema and hard exudation into the macular retina.
No specific treatment is indicated for these exudative maculopathies other than amelioration of the underlying problem when possible. When the underlying cause is systemic arterial hypertension, resolution of the hard exudate usually occurs within weeks to months after the blood pressure returns to normal.
Recently, systemic infection with Bartonella henselae has been associated with unilateral or bilateral optic disc edema and secondary serous macular detachment.  B. henselae is the causative organism of cat-scratch disease and a history of close
Figure 132-11 Pigmented peripapillary choroidal neovascular membrane developing in an eye with optic nerve head drusen.
Figure 132-12 Macular hard exudate secondary to marked chronic leakage of plasma from the optic nerve head in an eye with radiation-induced optic neuropathy.
contact with cats, especially kittens, may be elicited. Diagnosis is made by measuring serum antibody titers for B. henselae. Treatment with systemic tetracycline or ciprofloxacin may be successful.
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