Since 1898, when Haas reported the first case of X-linked retinoschisis,1 this condition and its ocular features have become more commonly recognized. The pathognomonic sign of X-linked retinoschisis is foveal retinoschisis, characterized by a "cartwheel"-like configuration of cystoid changes, radial folds, and perifoveolar microcysts. In approximately 50% of patients with X-linked retinoschisis, the foveal change is the only observed abnormality.2 However, inferotemporal peripheral retinoschisis may also be present. Other reported findings include arborescent and dendriform retinal structures, vascular sheathing, vascularized veils in the vitreous (which may bleed, causing vitreous hemorrhage), pseudopapillitis, grayish-white pigmentary changes in the retina suggestive of old chorioretinitis, and optic disc and/or peripheral retinal neovascularization.3"7 Rarely is retinal detachment present.8,9 We report two cases of X-linked retinoschisis associated with Coats'-like massive retinal detachments.
Case 1. This patient, who is currently 22 years old, was first seen at the age of 7 months with large-angle esotropia and horizontal pendular nystagmus. His family history was significant for two uncles with X-linked retinoschisis. He had the ability to fix and follow with his left eye, but not with his right eye. An examination was performed while he was under anesthesia. Cycloplegic refraction revealed refractive errors of +4.00 D in each eye. The results of an anterior segment examination and measurements of intraocular pressure were normal in each eye. In the right eye, there were two separate schisis cavities with hemorrhage along the inferior border of the inferior elevation. The left eye showed a bullous "dumbbell"-shaped retinoschisis, covering the temporal and inferior periphery. Adjacent to the elevated retina in both eyes were multiple areas of scattered intraretinal hemorrhages. The maculas of both eyes showed irregular foveal reflexes with pigment motding. In addition, the left eye showed granular yellow deposits in the macula.
At 9 years of age, the patient had visual acuities of 20/200 in each eye. A dilated fundus examination and fundus photography were performed. The right eye showed a dome-shaped inferior peripheral retinal elevation. The macula showed changes consistent with Xlinked retinoschisis, and evidence of dragging temporally and inferiorly (Fig. 1). The retina of the left eye showed flattening of the retinoschisis, and the appearance of macular pigmentary changes. Overlying this area of retinal pigment epithelial hypertrophy were cystic changes, also consistent with foveal retinoschisis.
Figure 1. Case 1. Right macula showing changes consistent with X-linked retinoschisis and evidence of dragging
Figure 2. Case 1 . Areas of intraretinal exudate anterior to bullous retinal detachment.
At 15 years of age, the patient s visual acuity was 20/200 in the right eye and 20/400 in the left eye. A dilated fundus examination of the right eye showed vascular sheathing and extensive cystic macular changes. Inferiorly, there was a large exudative retinal detachment overlying a pigmented red area. Vessels leading up to this pigmented red mass were engorged. Surrounding this detachment and mass, there were numerous areas of intraretinal exudate (Fig. 2). The left eye showed vascular sheathing, and elevation of the macula, which had been stable since the patient was 9 years old and essentially unchanged since an examination 6 years earlier.
At 21 years of age, the patients visual acuity was 20/400 in both eyes. A fundus examination of the right eye showed the same inferior retinal elevation with exudates. There were vitreous veils with associated retinal traction. During the course of several months, the areas of traction increased with secondary elevation of the temporal retina and then progressive elevation toward the center of the macula. A pars plana vitrectomy was performed with successful excision of the membranes, release of the traction, and flattening of the macula. Seven months postoperatively, the right macula remains stable with a visual acuity of 20/400.
Case 2. This patient, who is currendy 28 years old, was first found to have a subnormal visual acuity at age 5 when the diagnosis of X-linked retinoschisis was made. His family history was significant for one brother who was also diagnosed as having X-linked retinoschisis. Although the patients visual acuity was reduced at age 5, he felt that he was doing reasonably well until approximately 1 986 when he became aware of progressive loss of vision. The pertinent findings consisted of a lamellar or full-thickness hole in the right eye, retinoschisis, lipid exudation, and a vitreous hemorrhage in the left eye. He never received any treatment in either eye. When the patient was seen by one of us for the first time in 1989, his best-corrected visual acuity was 20/400 in each eye. The intraocular pressure was 12 mm Hg in each eye. The results of an anterior segment examination were remarkable only for some peripheral cortical lenticular changes, which did not appear visually significant.
A funduscopic examination showed changes consistent with X-linked retinoschisis inferotemporally in both eyes. Both optic nerves were pale. Additionally, sclerotic vessels were seen inferiorly, and a Coats'-like response was seen inferotemporally in the right eye. The macula was elevated with a large cystic central abnormality, including a probable stage III macular hole. In the left eye, there were cystic changes in the macula but not a full-thickness hole. There were, however, several large inner layer breaks in the schisis cavity at the 2- and 4-o'clock positions, along with a large exudative response in the peripheral retina. In this area, there appeared to be combined retinoschisis and retinal detachment.
It was thought that photocoagulation in areas of exudation would place the patient at risk for subsequent complications, and that vitrectomy for closure of the macular hole was unlikely to result in any improvement in vision. The patient was seen on several subsequent occasions. At age 27, angiomatous lesions with an exudative response were noted in the inferotemporal quadrant of the left eye, along with a small vitreous hemorrhage that layered below.
Figure 3. Case 2. Inferior retina of right eye showing typical dendriform structures.
On the patient's most recent visit, his visual acuity was 20/200 in the right eye and 20/400 in the left eye. The right eye remained unchanged during follow-up, whereas the left eye showed a course of intermittent vitreous hemorrhage.
Poor visual acuity is the most common reason why patients with X-linked retinoschisis present to their ophthalmologist. Visual acuities typically range from 20/50 to 20/400, but better acuities have been reported. A visual field examination usually shows a relative central scotoma and peripheral visual field defects corresponding to the areas of retinoschisis. Dark adaptation is not usually affected. Electroretinography (declined by both of our patients and their families) can be helpful and almost always shows diminished b-waves, with normal a-waves. The results of electro-oculography are normal in young patients, but tend to become abnormal with time and in severely affected individuals. On ophthalmoscopy, foveal retinoschisis is more common than peripheral retinoschisis. Tractional and exudative retinal detachment and vitreous hemorrhage have been reported, as well as success following vitreoretinal surgery.9,10
The molecular pathophysiology for X-linked retinoschisis has not yet been elucidated. However, the genetics of the disease are better understood. During the 1950s, the mode of transmission was determined to be sex linked. More recendy, the use of restriction fragment length polymorphism as a genetic marker has localized the gene for X-linked retinoschisis to the short arm of the X chromosome in the Xp22 region.11·12 This ability to indirecdy diagnose X-linked retinoschisis by DNA analysis may be useful for diagnosing cases with equivocal clinical findings, and for determining the carrier status in the female offspring of affected individuals and carrier mothers.
In both of our patients, the presence of the typical cystic foveal changes confirmed the diagnoses of Xlinked retinoschisis. In addition, the families of both patients contained male members with retinoschisis, whose relationship to each of our patients was consistent with X-linked recessive inheritance. The unusual feature demonstrated by both of our patients was the coexistence of peripheral massive exudative retinal detachments. Exudative changes were also observed in cases 4 and 5 of the series reported by Rosenfeld et al.9
Massive retinal exudation in the setting of Xlinked retinoschisis is the likely result of vascular incompetence, leading to leakage of serum products. The association of peripheral vascular anomalies has been well described in the literature. In 48 cases of Xlinked retinoschisis reported by Deutman, 8 cases (16.6%) demonstrated white, dendrite-like structures in the deeper layer of peripheral schisis.3 In a separate report, these structures were suggested to be vascular in origin.13 Other authors have reported similar dendrite-like structures surrounding an avascular peripheral temporal area, suggesting that these structures may represent pruned vascular trees or telangiectatic vessels.6 In case 2, these dendriform structures were noted in the inferior periphery of the right retina (Fig. 3). Aneurysmal formation in the schisis cavities in two individuals with X-linked retinoschisis has also been described.14 In another report, the presence of a retinal angioma was detected in a patient with Xlinked retinoschisis.15 Although no vascular anomaly was observed in one report of a blood-filled retinal cyst and exudative maculopathy in a patient with X-linked retinoschisis,16 this description may represent another outcome of vascular incompetence. On review of these previous observations, peripheral vascular anomalies are not unusual, but massive exudative retinal detachment resulting from such vascular incompetence has not been reponed. In our first case, the source of the massive exudation may have been the inferotemporal red mass seen at age 15.
Although no histopathologic examination of eyes with X-linked retinoschisis has demonstrated the presence of peripheral vascular anomalies, few studies of X-linked retinoschisis have been performed. In the study by Yanoff et al.,17 histopathology showed that the schisis occurred in the nerve fiber layer and not in the deeper retinal layers, as seen in degenerative retinoschisis. Such splitting may lead to degeneration of the retina, leading to isolation of the vascular elements in friable septa which would then be susceptible to vascular disruption and compromise. Supporting this hypothesis of vascular compromise are the observations of vitreous veils. In most reports of vitreous veils, retinal vascular elements are observed within the center of these sheets. However, the same inherited defect that leads to retinoschisis may also lead to the development of vascular anomalies. This is supported by the observation that retinal vessels that are normal on ophthalmoscopy often show delayed filling and leakage on fluorescein angiography. Regardless of the actual pathophysiology of the vascular leakage, massive exudation can occur, as demonstrated by our two cases.
The differential diagnoses of our two cases included familial exudative vitreoretinopathy, Coats' disease, and Goldmann- Favre disease. In familial exudative vitreoretinopathy, peripheral vascular dropout, arteriovenous shunts, and peripheral neovascularization are often seen. This disease and Coats' disease (retinal telangiectasia) were both considered, but neither can account for the observed foveal changes. In addition, Coats' disease is usually not a bilateral disease. Goldmann- Favre disease often demonstrates macular cystoid changes, but the cysts are usually coarser. Both of our patients had fine foveal changes and neither demonstrated the peripheral "bone- corpuscle" pigmentation or complained of nyctalopia, signs and symptoms often reported with Goldmann- Favre disease. Other diseases that should also be included in the differential diagnosis are Eales disease, juvenile macular degeneration, retinal periphlebitis, senile retinoschisis, sickle cell disease, Stargardt's disease, and Wagner's vitreoretinal dystrophy.
In summary, X-linked retinoschisis is a vitreoretinal dystrophy characterized by foveal retinoschisis, which is often associated with peripheral retinoschisis. Many associated retinal features have been described. This report documents the unusual manifestation of massive exudative retinal detachment associated with X-linked retinoschisis.
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