Multifocal retinopathy in Borna disease virus infected rabbits.

Experimental infection of rabbits with Borna disease virus led in all cases to a multifocal retinopathy that paralleled the clinical neurologic symptoms. The retinal changes always became evident first in the lower anterior quadrant of the eye. Infectious virus and antigen were detected in altered and unaltered regions of the retina. Individual chorioretinal lesions showed destruction of the pigment epithelium and the photoreceptors and perivascular inflammation close to small choroidal veins. Because of maximal antigen accumulation and the focal destruction of the retinal pigment epithelium we consider this cell layer to be the initially damaged structure.     

A microscopic study of herpes simplex virus retinopathy in mice

ICR white mice were inoculated with herpes simplex virus (HSV) type I in the anterior chamber of one eye. Animals were killed at intervals of 2, 4, 6, 8, and 10 days and both eyes were obtained for light and electron microscopic study of retinal changes. HSV retinopathy developed in 42 (91%) of 46 inoculated eyes. Fourteen (88%) of sixteen noninoculated eyes examined after the sixth postinoculation day developed HSV retinopathy. The earliest signs of retinopathy in the inoculated eye were peripheral retinal vasculitis and inflammatory cells throughout the nerve fiber layer on day 2. No virus was found in retinal tissue until day 4, at which time disruption of outer retinal layers (outer nuclear layer and layer of rods and cones) was observed in the peripheral retina. The earliest signs of retinopathy in the noninoculated eye were isolated foci of outer retinal disruption in the posterior retina on day 6. The inflammation accompanying early retinal changes of HSV retinopathy were more severe in the inoculated eye. Electron microscopy of both eyes revealed viral particles in the inner nuclear and ganglion cell layers at the time of outer retinal disruption, but viral particles were seen only rarely in the outer retinal layers at this stage. Early disruption of normal retinal architecture may be due to infection and destruction of Muller cells. The retinopathy progressed in both eyes to total destruction of the retina by day 10. Viral infection of the retinal pigment epithelium occurred, but viral particles were seen only rarely in the underlying choroid. This model may be useful for the study of HSV retinopathy in humans.     

Ocular and extraocular inflammation induced by immunization of tyrosinase related protein 1 and 2 in Lewis rats

Vogt-Koyanagi-Harada (VKH) disease is an ocular inflammatory disease and is considered to be a cell-mediated, autoimmune disease against melanocytes. To learn more about the mechanisms involved in VKH disease, the identification of the antigens specific to the disease and the development of an animal model are critically important. We have expressed and purified the melanocyte specific proteins, tyrosinase-related protein 1 (TRP1) and 2 (TRP2). Lewis rats developed an ocular and extraocular inflammatory disease 12 days after immunization with TRP1 or TRP2 that was characterized clinically by the infiltration of inflammatory cells and accumulation of massive fibrin in the anterior and posterior chambers of the eye. Histologically, inflammatory cells were found in the anterior and posterior chambers, iris, ciliary body, the choroid, subretinal space and vitreous body. In severe cases, a serous detachment of the retina was observed. In mild cases, focal inflammatory lesions surrounded by normal chorioretinal architecture were observed and the inflammation persisted for more than 42 days after the injection. Some eyes showed accumulation of epithelioid cells in the choroid or the retinal pigment epithelium which were similar to the Dalen-Fuchs nodules found in patients with VKH disease. The alterations of the photoreceptor outer segment and the outer nuclear layer were less severe than in experimental autoimmune uveitis induced by retinal antigens. Extraocular manifestations such as skin lesions and meningitis were also observed. The clinical course and histological findings in these rats resembled the changes in patients with VKH disease.     

Photodynamic therapy with verteporfin for subfoveal choroidal neovascularization in Vogt-Koyanagi-Harada syndrome

PURPOSE: To assess the role of photodynamic therapy using verteporfin in the treatment of subfoveal choroidal neovascularization in Vogt-Koyanagi-Harada syndrome. DESIGN: Interventional case report. METHODS: A 9-year-old patient with subfoveal choroidal neovascularization received a single photodynamic therapy with verteporfin session (one eye) and was prospectively followed with fluorescein angiography. RESULTS: A complete regression of the lesion was achieved within 1 week after treatment. Visual acuity improved from 20/800 to 20/320 by 6 months of follow-up. Fluorescein angiography disclosed unexpected retinal pigment epithelium alteration within the treatment area. CONCLUSION: Although regression of the choroidal neovascularization occurred, unpredicted findings involving normal retina in the vicinity of the lesion suggest that further studies are required to assess the clinical value of this treatment for subfoveal choroidal neovascularization in Vogt-Koyanagi-Harada syndrome.     

Tomographic features of serous retinal detachment in Vogt-Koyanagi-Harada syndrome.

To clarify the nature of serous retinal detachment in Vogt-Koyanagi-Harada (VKH) syndrome, 42 consecutive eyes of 21 patients with acute phase VKH syndrome were examined using optical coherence tomography (OCT). OCT revealed two patterns of serous retinal detachment. Twenty-nine eyes (69%) had a true retinal detachment, 17 eyes (40%) had intraretinal fluid accumulation in the outer retina, and 4 eyes had both. Intraretinal fluid accumulation appeared as an oval space in the outer retina. On fluorescein angiography, the eyes with intraretinal fluid accumulation showed more severe dye leakage from the retinal pigment epithelium.     

Multifocal posterior uveitis: clinical and pathological findings.

A pathological study was performed on the necropsy eyes of a 59-year old-woman who had suffered for nine years from multifocal posterior uveitis. The disease had been controlled by steroid therapy with good preservation of visual function. Extensive investigation did not reveal the aetiology. On macroscopic examination numerous focal lesions with various degrees of pigmentation were observed scattered across the fundi. These lesions were studied by light and electron microscopy and immunohistochemistry. There was ongoing chorioretinal inflammation in the foci, producing destruction of Bruch's membrane, the retinal pigment epithelium (RPE), and the outer retina. The focal scars showed migration of RPE and glial cells and neovascularisation. Capillary and venule endothelial cells were swollen at the inflammatory sites. Attempts to establish a cause for this condition were unsuccessful.     

Chorioretinal lesions in chronic granulomatous disease of childhood. Clinicopathologic correlations

The authors examined an eye obtained post-mortem from a patient with chronic granulomatous disease of childhood and clinically apparent chorioretinal scars. Histologic examination disclosed numerous chorioretinal scars with associated retinal pigment epithelial changes and glial proliferation. Special stains for bacteria and fungi were negative. Additional findings were scattered pigment-containing macrophages found in the patient's spleen, liver, lymph nodes, bone marrow, lungs, kidney, thymus, choroid, and retina. The significance of the pigmented macrophages is unknown, however they may represent an abortive macrophage response to infectious agents.     

Subretinal neovascularization in the Vogt-Koyanagi-Harada syndrome

Two Hispanic patients with Vogt-Koyanagi-Harada (VKH) syndrome each developed a disciform lesion involving the macula of one eye several months after the onset of symptoms. Each had extraocular manifestations which included pleocytosis of the cerebrospinal fluid. The disciform lesions were associated with retinochoroidal anastomoses, a finding not previously reported in VKH syndrome. Each patient had a separate extramacular disciform lesion in the same eye. Two other Hispanic patients with diffuse bilateral intraocular inflammation had ocular findings consistent with VKH syndrome. One of these patients developed bilateral peripapillary disciform lesions and the other developed a disciform macular scar in one eye. Fluorescein angiography in each patient showed early irregular hyperfluorescence with late intense staining. The disciform detachments occurred in areas of reactive proliferation of the retinal pigment epithelium, and we postulate that growth of subretinal new vessels occurred through areas of Bruch's membrane that were damaged by the inflammation.     

Hereditary pigmented paravenous chorioretinal atrophy

Pigmented paravenous chorioretinal atrophy PPCRA) is a rare disorder which is diagnosed primarily because of the typical fundoscopic appearance of retinal pigment epithelial (RPE) atrophy and clumping in a paravenous distribution. A mildly affected and asymptomatic 54-year-old mother and her mildly affected daughter and severely affected son presented with pigmented paravenous chorioretinal atrophy. The severely affected (proband) 28-year-old man manifested the characteristic paravenous chorioretinal atrophy with pigment clusters in both eyes with macular involvement. Besides the characteristic fundus picture, he also had chronic angle closure glaucoma. His 23-year-old sister presented with unilateral involvement. Her right eye showed focal perivenular retinal pigment epithelial hyperplasia at the 2 o'clock position and dilated, tortuous retinal veins, while her left eye had only dilated and tortuous retinal veins. Both patients were hyperopic. Their mother had an area of chorioretinal atrophy in one eye near a retinal vein. The scotopic ERG responses were markedly abnormal in the male patient, while his sister had a mild decrease in amplitude of both a and b waves in both eyes. One of the children of an unaffected family member was found to have dilated and tortuous retinal veins and hyperopia (III-12). To our knowledge, this is the fourth report of familial occurrence of pigmented paravenous chorioretinal atrophy. The present pedigree is compatible with X-linked recessive or dominant inheritance.     

Choroideremia: a clinical, electron microscopic, and biochemical report

An asymptomatic 19-year-old male with choroideremia had diffuse loss of retinal pigment epithelium (RPE) and choroid except for the periphery and macula. Fluorescein angiography of the arteriovenous phase showed absence of retinal pigment epithelium and exaggerated visualization of choroidal vessels in involved areas. The mother was a typical carrier with pigment stippling of the midperipheral retina. Histopathologic examination of affected areas of one eye showed marked degeneration of the outer and midretina with loss of retinal pigment epithelium and Bruch's membrane, absence of choriocapillaris, chorioretinal adhesions and gliosis. Atrophy of inner and mid-choroid was also observed. Pigmented macrophage-like cells had migrated into the outer and midretinal layers. Electron microscopy disclosed macrophage-like cells with trilaminar structures and photoreceptor phagosomes in the RPE and outer retina. Remnants of photoreceptor outer segments were adherent to the plasma membranes of the macrophage-like cells. Biochemical analysis of retinal tissue samples for interphotoreceptor retinoid-binding protein (IRBP) showed marked reduction in the 146K bands in the equator and posterior pole in the patient compared to controls. Cyclic nucleotide content was altered in the retinal equator. Cyclic AMP was several-fold higher in the RPE-choroid complex of the affected eye than in the control.     

Glioneuroma associated with colobomatous dysplasia of the anterior uvea and retina. A case simulating medulloepithelioma

The left eye of an otherwise healthy child was enucleated at the age of 2 months because of an enlarging mass involving the temporal iris, ciliary body, and anterior retina. The initial histopathologic diagnosis was malignant medulloepithelioma with orbital extension. Closer study revealed a superotemporal chorioretinal and ciliary body coloboma; dysplasia of the adjacent retina; a glioneuromatous mass replacing the temporal ciliary body, chamber angle structures, and iris and extending through the sclera to involve the insertion of the lateral rectus muscle; neuroepithelial elements resembling medulloepithelioma; and abnormally developed iris pigment epithelium, and dilator and sphincter muscles. Immunohistochemistry demonstrated that the main mass consisted of neurons positive for neuron-specific enolase (NSE), synaptophysin and neurofilaments, and glial cells expressing vimentin, glial fibrillary acidic protein, and S-100 protein. The neuroepithelial elements reacted positively for cytokeratins and S-100 protein, in addition to NSE and vimentin, suggesting ciliary epithelial rather than embryonic retinal origin. The tumor was rediagnosed as glioneuroma, which in this case was part of a widespread colobomatous dysplasia of the anterior uvea and retina. The patient is alive without metastases or local recurrence 2 years following enucleation and subtotal removal of the lesion.     

Neurofibromatosis 2 leads to choroidal hyperfluorescence in fluorescein angiography

Background For the diagnosis of NF 2, ocular findings like juvenile cataract, retinal and combined hamartomas of the retinal pigment epithelium and the retina as well as tumours of the optic nerve play an important role. An early diagnosis is essential in order to inhibit deafness from bilateral vestibular schwannoma. But sometimes the Manchester diagnostic criteria for NF2 are not completely fulfilled. Frequently, suspicious macular anatomy is found in neurofibromatosis 2 (NF2) patients. We hypothesise that the underlying retinal pigment epithelium or the retina of the macular region alters in NF2 patients. Therefore, we have tested by fluorescence angiography whether NF2 is associated with chorioretinal changes. Methods and patients In a prospective study, 48 patients matching the criteria for NF2 with known genotype underwent a complete ophthalmic examination including funduscopy and fluorescence angiography. The influence of the genotype was statistically analysed by odds ratios and their 95% confidence intervals. Results Eleven eyes of nine patients showed choroidal hyperfluorescence in the macular region on fluorescence angiography. There was staining spreading from grainy hyperfluorescence to minor variants of a combined hamartoma of the retina and the retinal pigment epithelium. All of these manifestations presented without leakage in the late angiographic phases. These choroidal findings were present in one patient with frameshift mutation, in two patients with nonsense mutations and in six patients with splice site mutations of the NF2 gene. The statistical analysis showed a significant lower risk of choroidal alterations in patients with somatic mosaicism, deletions and unfound mutations. Conclusion Using fluorescence angiography pathological changes of the macular region can be detected in NF2 patients. The ophthalmic examination, which often is limited to the anterior eye segment, may play a role in finding the diagnosis in incomplete NIH criteria. The presented study shows chorioretinal hyperfluorecences without leakage of the macular region, which might be considered as a forme fruste of a hamartoma. Choroidal hyperfluorescences add to the spectrum of genotype-phenotype correlations in NF2. Grant information: Supported in part by Deutsche Krebshilfe 70–2450-Ma2 to VFM and LK. Sequencing was done on an ABI310 sequencer donated by the Rodulf Bartling Stiftung.     

Multiple recurrent serosanguineous retinal pigment epithelial detachments in black women

Three middle-aged black women suffered recurrent, multiple, bilateral, asymmetric, serosanguineous retinal pigment epithelial detachments. These involved the posterior fundus with resolution and recurrences producing subretinal hemorrhages, vitreous hemorrhages, retinal pigment epithelial pigmentary mottling, and chorioretinal scars. Fluorescein angiography showed evidence of choroidal neovascular membranes, choroidal serosanguineous leaks, or both. Ocular inflammation was not evident. Systemic laboratory tests were noncontributory. The clinical pattern was not characteristic of any other entity producing serosanguineous retinal pigment epithelial detachments. The origin remains to be defined.     

Surgical management of bilateral exudative retinal detachment associated with central serous chorioretinopathy

PURPOSE: To report a case of bilateral bullous exudative retinal detachment in central serous chorioretinopathy (CSC) which was attached by vitrectomy and internal drainage of the subretinal fluid. METHODS: A 47-year-old man affected by bilateral atypical CSC with a bullous retinal detachment with subretinal exudate. A fluorescein angiogram (FAG) showed multiple points of leakage and staining of subretinal fibrosis. A tentative diagnosis of Vogt-Koyanagi-Harada (VKH) syndrome was made and the patient was treated with systemic corticosteroids and immunosuppressive agents. However, the subretinal fluid was not absorbed. He was then treated with vitrectomy and internal drainage of subretinal fluid. RESULTS: The retina was attached successfully in both eyes. Visual acuity improved to 20/50 in his left eye but did not improve in the right eye due to subretinal fibrotic scarring and atropic changes on the macula. CONCLUSIONS: Our case suggests that the surgical management of bullous exudative retinal detachment is safe and necessary.     

Longitudinal study of lesions of the posterior segment in onchocerciasis

Onchocerciasis is a major cause of blindness, and much of the blindness due to onchocerciasis is caused by chorioretinitis. Little is known about the progression of lesions in the posterior segment in either untreated or treated disease. The authors studied the progression of onchocercal chorioretinitis in 57 patients from 1 to 3 years. Changes were documented from detailed ocular examinations, fundus photographs, and fluorescein angiograms, and included live intraretinal microfilariae, intraretinal hemorrhages, cotton-wool opacities, intraretinal pigment, white and shiny intraretinal deposits, retinal pigment epithelial window defects, and atrophy. Depigmentation at the edge of chorioretinal scarring progressed at a rate of up to 200 microns per year. Ivermectin or mebendazole treatment did not appear to alter the progress of depigmentation at the edge of chorioretinal scars. These observations suggest that onchocercal chorioretinitis is associated with early changes in the retina and retinal pigment epithelium, and that disease in the posterior segment may progress rapidly.     

Dose-related structural effects of photodynamic therapy on choroidal and retinal structures of human eyes

PURPOSE: To determine the effects of photodynamic therapy (PDT) on choroidal and retinal structures of human eyes. METHODS: One eye from each of three patients with large malignant melanomas of the uvea destined for enucleation received PDT using verteporfin according to the approved treatment recommendations for patients with age-related macular degeneration. Two laser spots and two light doses (50 J/cm(2) and 100 J/cm(2)) were applied in unaffected chorioretinal areas. The effects of PDT were assessed by fluorescein and indocyanine-green angiography. The eyes were enucleated 1 week later, fixed in buffered paraformaldehyde/glutaraldehyde solution, bisected along the laser spots, and processed for light and electron microscopy. RESULTS: In agreement with the clinical angiographic findings of hypofluorescence, a rather selective occlusion of the choriocapillary layer was observed in the 50-J/cm(2) PDT areas, whereas the 100-J/cm(2) PDT areas additionally revealed closure of deeper choroidal vessels and focal alterations of the retinal pigment epithelium. The overlying neurosensory retina, including photoreceptors and retinal capillaries, was well preserved in all PDT areas. Electron microscopy showed that alterations of the choriocapillary endothelium comprised swelling, shrinkage and fragmentation of endothelial cells, detachment from their basement membrane up to complete degeneration of the endothelial lining, leading to platelet aggregation, degranulation, and thrombus formation. Complete occlusion of capillary lumina by fibrin, thrombocytes, and cellular debris was observed. Remaining intact endothelial cells appeared to be reorganized into novel smaller vascular channels within occluded lumina. CONCLUSIONS: PDT with verteporfin at a dosage used clinically induces selective occlusion of the physiological choriocapillaris without affecting deeper choroidal, retinal, and optic nerve vessels or the overlying retinal pigment epithelium and neurosensory retina. The main mechanism of action appears to be vascular thrombosis induced by cytotoxic damage of endothelial cells and platelet activation. An increase in light dose enhances the occlusive effect with thrombosis within deeper choroidal layers and damage to the retinal pigment epithelium. However, photoreceptors remained intact at all light doses used.     

色素性静脉旁脉络膜视网膜萎缩

目的探讨色素性静脉旁脉络膜视网膜萎缩（PPCRA）患者的临床特点和相关意义。方法回顾分析2例PPCRA患者的临床资料。结果1例双眼患病者眼底均见特征性的沿视网膜静脉分布色素沉着和脉络膜萎缩;1例单眼患病者右眼底沿颞侧上下静脉旁有散在色素沉着,有不典型的局限性脉络膜萎缩。FFA显示沿视网膜血管弓有散在的遮蔽荧光和斑驳样荧光改变。结论PPCRA发病多为双眼,眼底呈特征性改变,也可单眼发病,两侧的眼底表现可以不一致。     

Idiopathic and secondary chorioretinal folds]

Chorioretinal folds may be observed in many choroidal or retinal diseases. In age-related macular degeneration, they are usually associated with retraction of a neovascular membrane and a typically radial pattern of the folds can be seen. In this disease, pigment epithelium folds were recently described. Their clinical and angiographical characteristics are different from chorioretinal folds and the two diseases should not be confused. A 74-old patient presented, in the left eye, with sub foveal new vessels situated at the center of a pigment epithelial detachment (PED). Radial chorioretinal folds surrounded the PED, as frequently observed during follow-up in subretinal neovascular membranes. Nevertheless, right eye fundus examination revealed roughly horizontal, regular and parallel chorioretinal folds. Ultrasonography demonstrated characteristics of idiopathic chorioretinal folds: flattening and thickening of the posterior sclera and choroid. No sign of posterior scleritis was found. These ultrasonographic elements were observed in the left eye away from the central neovascular membrane. The chorioretinal folds therefore seemed to be idiopathic, in a hyperopic patient. The shape of the folds was modified in one eye by a subfoveal neovascular membrane. Chorioretinal folds may occur in different retinal diseases. The associations with many different aetiologies with modification of the shape of the folds, as described in this clinical case, should be emphasized.     

Depigmented atrophic lesions in sunset glow fundi of Vogt-Koyanagi-Harada disease

PURPOSE: Although the depigmented, small, round to oval lesions seen in the sunset glow fundi of Vogt-Koyanagi-Harada disease are considered to represent Dalén-Fuchs nodules, there is no histopathologic evidence to support such a consideration. An attempt is made herein to clarify the nature of the atrophic lesions and distinguish them from Dalén-Fuchs nodules seen in eyes with Vogt-Koyanagi-Harada disease. METHODS: Eyes from five individuals with clinical diagnoses of Vogt-Koyanagi-Harada disease were subjected to histopathologic examination. The retinal pigment epithelial changes from early active to convalescent and late chronic recurrent stages were evaluated. Particular attention was paid to Dalén-Fuchs nodules, depigmented lesions in the sunset glow fundi, and hyperpigmentation of the chronic recurrent stage. RESULTS: Eyes of two individuals, one in the active stage of Vogt-Koyanagi-Harada disease and the other in the convalescent stage, showed the presence of Dalén-Fuchs nodules. The depigmented small retinal pigment epithelial lesions were seen in two individuals, both of whom exhibited the sunset glow fundus of the convalescent stage. The retinal pigment epithelial lesions represented damage or disappearance of retinal pigment epithelial cells, and the sunset glow fundus appearance was from the loss of choroidal melanocytes. The heavy pigmentation seen in fundi with the chronic recurrent stage was the result of the proliferation of retinal pigment epithelial cells. CONCLUSION: The Dalén-Fuchs nodule is a specific histologic change observed at the level of retinal pigment epithelium in patients with Vogt-Koyanagi-Harada disease. There is no histologic confirmation that the depigmented small atrophic lesions seen in the sunset glow fundi of Vogt-Koyanagi-Harada disease are Dalén-Fuchs nodules. The depigmented lesions represent localized damage or disappearance of retinal pigment epithelial cells.     

Atypical central lesions in serpiginous choroiditis treated with oral prednisone

• Purpose: To demonstrate the effect of oral prednisone in the treatment of atypical isolated central lesions in two patients with serpiginous choroiditis. • Methods: Two patients with a history of serpiginous choroiditis in the fellow eye developed an isolated central lesion. One patient showed combined detachment of the retinal pigment epithelium and serous detachment of the retina, while the other showed thickening of the retinal pigment epithelium and shallow detachment of the retina. Both patients were treated with 80 mg/day of oral prednisone. • Results: In both patients regression of the lesion and improvement of visual acuity was achieved within several days with- out the development of a chorioretinal scar. In one patient the le- sion recurred after discontinuation of the prednisone. With continuation of a low dose of prednisone for sev- eral months definite regression of the esion and improvement of visual acuity to near-normal values was achieved in both patients. • Conclusion: In two patients with visual loss due to an atypical central lesion in serpiginous choroiditis, regression of the lesion without the development of a typical chorioretinal scar and subsequent improvement of visual acuity was achieved with the administration of oral prednisone. Received: 3 January 1997 Revised version received: 23 June 1997 Accepted: 1 July 1997