Bilateral blindness and lumbosacral myelopathy associated with high-dose carmustine and cisplatin therapy

PURPOSE: To report the early ocular pathologic findings associated with high-dose carmustine and cisplatin therapy. METHODS: A patient with metastatic breast carcinoma developed an acute onset of branch retinal artery occlusion, bilateral blindness, and a myelopathy involving the lower extremities after high-dose chemotherapy and bone marrow transplant. RESULTS: Histopathologic examination of the eye and optic nerves at autopsy disclosed nerve fiber layer infarction secondary to right inferior temporal retinal artery thrombosis. Patchy necrosis of both optic nerves, medulla oblongata, and spinal cord was associated with focal small-vessel thrombosis. CONCLUSIONS: The syndrome of retinal vascular occlusion, optic neuropathy, and myelopathy is associated with the high-dose chemotherapeutic agents carmustine and cisplatin. The distribution of necrosis suggests an ischemic event rather than direct neurotoxic effects.     

Clinicopathologic correlation of retinal to choroidal venous collaterals of the optic nerve head

An optic nerve meningioma developed in an elderly woman and was followed for 13 years until her death. The optic nerve was initially normal. Over time it became swollen and then atrophic and developed retinal venous to choroidal venous collaterals. Five hundred serial sections were prepared through the optic nerve and for approximately 1.5 mm superiorly and inferiorly to the optic nerve to trace the course of the collaterals that were seen ophthalmoscopically and angiographically in the optic nerve head. This clinicopathologic study shows clearly that the abnormal channels are, in fact, retinal venous to choroidal venous collaterals (bypass channels). Four collaterals extended around the end of Bruch's membrane at the optic nerve head. Two more collaterals extended through the retinal pigment epithelium to become continuous with a subretinal pigment epithelial neovascular membrane, the vessels of which connected with the choroidal vessels through a defect in Bruch's membrane.     

Evulsion of the retina associated with optic nerve evulsion

We examined two patients with optic nerve evulsion as well as nasal peripapillary retinal and retinal pigment epithelial evulsion after ocular trauma. Fluorescein angiography demonstrated an intact peripapillary choriocapillaris, loss of peripapillary retina and retinal pigment epithelium, and complete disruption of retinal perfusion. We have postulated a mechanism for traumatic peripapillary retinal evulsion involving severe anterior displacement and abduction of the globe that may explain how the disruptive force was transmitted to the nasal retinal nerve fiber layer. We have provided a clinical correlation with magnetic resonance imaging of the optic nerve and globe of a normal individual.     

Visual sensory disorders in congenital nystagmus

Congenital nystagmus (CN) is a common disorder indicative of a primary disturbance of the ocular motor or visual sensory systems. The authors prospectively evaluated 81 patients with CN, structurally normal eyes, and minimal or no abnormalities of the optic nerve, macula, and retinal pigment epithelium (RPE). Seventy-four (91%) patients were found to have a disorder of the visual sensory system. Thirty-four patients had albinism, 37 had a congenital or early onset disorder of the retinal photoreceptors, and 3 had abnormalities of the optic nerve. The remaining seven (9%) patients had motor CN. Most patients presenting with CN have visual loss and should be evaluated for an underlying disorder of the visual sensory system.     

Noninvasive diagnosis and ophthalmic features of mucolipidosis type IV

OBJECTIVE: To comprehensively describe the ophthalmic characteristics of patients with mucolipidosis type IV. DESIGN: Prospective natural history study. PARTICIPANTS: Twenty-two patients with confirmed mucolipidosis type IV. METHODS OR TESTING: External and slit-lamp examination with dilated funduscopy, photography of corneal and retinal lesions, and exfoliative conjunctival cytology were performed. MAIN OUTCOME MEASURES: Grading of corneal, optic nerve, retinal vasculature, and pigmentary abnormalities. RESULTS: All patients exhibited some degree of corneal epithelial haze, optic nerve pallor, retinal vascular attenuation, and retinal pigment epithelial changes. The associated ocular findings observed in decreasing order of frequency were strabismus, corneal erosion, cataract, corneal abnormalities, fundus abnormalities, and ptosis. The older patients were significantly more likely to demonstrate severe optic nerve pallor, retinal vascular attenuation, and corneal epithelial haze. Conjunctival cytologic studies showed characteristic lysosomal inclusions on light and electron microscopy. CONCLUSIONS: Patients with mucolipidosis type IV have characteristic ophthalmic features, most of which have a progressive course. Conjunctival cytologic studies help confirm the diagnosis of this disorder.     

Vitreal pathogenic role in optic pit foveolar retinoschisis and central serous chorioretinopathy

Purpose: To expand on current theories concerning the vitreal‐induced mechanism underlying the development of foveolar retinoschisis and macular sensory detachments associated with optic nerve head pits. To propose the notion that vitreal traction may contribute to the pathogenesis of serous detachments in central serous chorioretinopathy (CSC). Reports: We describe two patients, one with macular retinoschisis and the other with central serous detachment. The first patient, a 45‐year‐old Hispanic female, presented with a temporally located optic nerve head pit, foveolar retinoschisis and schisis retinal spaces extending to the surrounding macula and to the disc. The second patient, a 43‐year‐old Haitian male, developed a central serous retinal detachment OS with decreased visual acuity one day following in‐office administration of Apraclonidine (0.5 per cent Iopidine, Alcon) and Dorzolamide‐Timolol Maleate (Cosopt, Merck) to lower elevated intraocular pressure (IOP). Macular retinal pigment mottling and epiretinal membrane sheen OU had been observed on his initial visit. Visual acuity improved within a three day period with resolution of the serous detachment. Conclusion: We suggest that the persistence of Cloquet's canal may permit fluid leakage into the proximal vitreous in cases of congenital optic nerve head pits. Tangential vitreal traction may promote the opening of a fistula at the optic pit and additionally thrust vitreal fluid into the pit and retinal space inducing the formation of schisis spaces, foveolar‐schisis and underlying sensory serous detachment. We question whether a reduction in vitreous volume, induced by initial administration of anti‐glaucoma medications, may contribute to the development and/or recurrence of central serous choroidopathy in predisposed individuals.     

Pigmented adenoma of the optic nerve head simulating a melanocytoma.

PURPOSE: The purpose of this report is to describe a clinicopathologic correlation of an unusual pigmented tumor of the optic nerve head, to point out that such a lesion can simulate clinically a melanocytoma of the optic disc, and to discuss the differential diagnosis of pigmented epipapillary lesions. FINDINGS: Histopathologic studies of the affected eye showed a peculiar pigmented tumor of the optic disc that was compatible with an adenoma arising from the juxtapapillary retinal pigment epithelium. CONCLUSIONS: Adenoma of the retinal pigment epithelium can closely simulate a melanocytoma of the optic disc. There are some clinical features that may serve to differentiate the two lesions.     

A child with unilateral disk elevation

A healthy 7-year-old girl underwent a routine eye examination and was referred for unilateral, left optic nerve swelling. Best-corrected visual acuity in the affected eye was 20/20 with full Ishihara color plates and no relative afferent pupillary defect. Initial extensive workup was normal for any cause of unilateral disk swelling. When the patient returned a few years later with decreased vision, a thickened, gray-white preretinal tissue with surrounding retinal contraction and a surrounding charcoal gray lesion had developed in her optic nerve. Spectral-domain optical coherence tomography over the optic nerve demonstrated distortion of the inner retinal architecture, a dense epiretinal membrane, and high internal reflectivity. Clinical examination and imaging revealed a diagnosis of combined hamartoma of the retina and retinal pigment epithelium.     

Changes in the juxtapapillary retinal pigment epithelium following intravenous injection of sodium iodate. A light and electron microscopic study using horseradish peroxidase as a tracer

The effect of an intravenous injection of sodium iodate on the retinal pigment epithelium immediately surrounding the optic nerve head has been investigated using horseradish peroxidase as a morphological tracer. A sodium iodate injection leads to a necrotic reaction of practically the complete retinal pigment epithelium. The juxtapapillary pigment epithelium, however, showed only attenuation and depigmentation without any necrotic reaction 4 and 12 days after the injection. Twenty-six days following the injection the epithelium had almost normalized. The result of this study thus demonstrates a noteworthy resistance of the juxtapapillary retinal pigment epithelium against the sodium iodate effect. At no stage was there a clear indication of a breakdown of the permeability barrier constituted by the juxtapapillary retinal pigment epithelium. Horseradish peroxidase moved into the peripapillary sensory retina by lateral diffusion from the surrounding retina and diffused into the optic nerve head proper, confirming the presence of a diffusional pathway through the Kuhnt intermediary tissue.     

Linear pattern of West Nile virus-associated chorioretinitis is related to retinal nerve fibres organization

PURPOSE: To clarify the reason for the linear pattern of West Nile virus (WNV)-associated chorioretinitis. METHODS: The study included 12 patients (24 eyes) with WNV-associated chorioretinitis. All the patients underwent a complete ophthalmic evaluation, including dilated fundus examination, fundus photography, fluorescein angiography, and indocyanine green angiography. Characteristics of linear streaks, particularly their relationship to the course of retinal and choroidal vessels, and pattern of retinal nerve fibres, were analysed. RESULTS: All patients had bilateral multifocal chorioretinitis with linear clustering of chorioretinal lesions associated with a variable number of scattered lesions. Linear streaks, variable in number and length, originated from the optic disc or its vicinity in most cases. Their course in all cases appeared to closely follow the course of retinal nerve fibres, rather than that of retinal or choroidal vessels. CONCLUSIONS: Results of our study show that the linear pattern of WNV-associated chorioretinitis is related to retinal nerve fibres organization, suggesting a contiguous spread of WNV virus from central nerve system via the optic nerve fibres to the outer retina, retinal pigment epithelium, and choroid.     

MORNING GLORY SYNDROME: A REPORT OF TWO CASES

Two cases of Morning Glory Syndrome are presented to draw attention to the occurrence of this rare syndrome in Australia. The typical case shows an enlarged excavated optic nerve head surrounded by peripapillary pigment disturbance. There is early branching of the retinal vessels and a central tuft in the cavity. Some management guidelines are suggested.     

Clinical and electrophysiological features of tilted disc syndrome

Nine patients with tilted disc syndrome were examined psychophysically and electrophysiologically. Visual field defects did not correspond to fundus abnormalities in half of the eyes. Visual evoked responses were more reduced than electroretinogram responses. These results indicate that associated visual field defects and impairment of visual acuity were related not only to a localized staphylomatous ectasia of the posterior globe but also to a lesion of the inner retinal layer, optic nerve, or more proximal visual pathway. This suggests that a developmental abnormality in the embryonic retina may result in hypoplasia of the retinal pigment epithelium and neural elements as well as an anomaly of the optic disc. Investigation of visual function in patients with tilted disc syndrome may help to identify possible concomitant retinal and optic nerve dysfunction.     

细胞因子对视神经损伤修复作用的研究进展

创伤、代谢、高眼压等多种因素均可能造成视网膜神经节细胞和或视神经损伤，而视网膜神经节细胞损伤凋亡后无法自主再生，因此往往会造成视力下降甚至丧失等严重后果。对于视神经损伤，目前临床上尚无非常有效的治疗方法。近年有研究发现细胞因子可以明显促进视网膜神经节细胞的存活和轴突再生。本文就其中睫状神经营养因子、胶质源性神经营养因子、色素上皮衍生因子、粒细胞集落刺激因子、血浆凝血因子、促红细胞生成素等几种细胞因子促进视神经损伤修复作用的研究进展进行综述。     

Therapy of arterial vascular occlusions of retinal and optic nerve (author's transl)

The authors report on 136 cases of arterial occlusion (80 patients suffering from occlusion of the retinal vessels and 56 patients with vascular occlusion in the optic nerve) who were treated with the vasoactive xanthic substance Pentoxifylline (Trental). A part from its positive effect on the vascular circulation, Trental also helps to improve microcirculation in the retinal and optic nerve tissue damaged by hypoxia. After a 2-week infusion therapy with additional digitalisation, treatment was continued for another 3-6 months with oral administration of Trental 400. In 50 cases therapy was combined with the systemic administration of corticosteroids. Under the mentioned therapy a definitely improved visual acuity (at least 3 lines on the eye charts) was achieved in 56% of the cases with occlusion of the retinal vessels and in 51% of the cases with vascular occlusion in the optic nerve, i.e., in 54% of the total number of patients. Whether or not the additional administration of corticosteroids helped to this effect was not proved.     

Ocular histopathologic studies of neonatal and childhood adrenoleukodystrophy

Histopathologic studies of the eyes of one patient (a boy who died at 14 years of age) with childhood adrenoleukodystrophy and two patients (girls who died at 24 and 31 months of age) with neonatal adrenoleukodystrophy showed the accumulation of the characteristic bileaflet inclusions in optic nerve macrophages, retinal neurons, and macrophages and loss of ganglion cell and nerve fiber layer. Additionally, in the two cases of neonatal adrenoleukodystrophy, changes resembling early retinitis pigmentosa were found, with accumulation of characteristic inclusions in the retinal pigment epithelium and pigment-laden macrophages. One of the patients with neonatal adrenoleukodystrophy also had an anterior subcapsular cataract and cystoid macular edema.     

A defect in the blood-retina barrier in the optic nerve head region in the rabbit and the monkey

The permeability properties of the tissues in the optic nerve head region have been investigated in monkey and rabbit using horseradish peroxidase as an histochemical tracer. Following intravenous administration, the tracer diffused from the peripapillary choroid into the different parts of the optic nerve head region, and also into the receptor layer of the sensory retina adjacent of Kuhnt intermediary tissue. This observation demonstrates a defect in the blood-retina barrier in this region. The defect in the permeability barrier is most likely located either to the retinal pigment epithelium near the optic nerve head, to the Kuhnt intermediary tissue, or to the junction between these tissues.     

OCT in successful surgery of retinal detachment associated with optic nerve head pit

The authors describe the course of a patient with retinal detachment associated with optic nerve head pit for whom optical coherence tomography (OCT) was performed before and after vitrectomy and gas tamponade. An 18-year-old woman presented with macular elevation and a lamellar macular hole associated with optic nerve head pit. OCT showed that the retinal elevation consisted of both separation of the inner and outer retinal layers and detachment of the outer layers from the retinal pigment epithelium. After vitreous surgery and postoperative intraocular gas tamponade, the macular elevation gradually resolved, and OCT showed that improvement in central vision corresponded with flattening of the outer layer detachment in the fovea. OCT is a useful tool for monitoring the therapeutic effect of vitrectomy and gas tamponade for retinal detachment associated with optic nerve head pit.     

Follow-up of proliferation of juxtapapillary retinal pigment epithelium

Purpose: Bengin proliferation of the juxtapapillary retinal pigment epithelium is a rare but important tumor because it may be mistaken for a malignant lesion such as choroidal melanoma. Case report: A 9-year-old male patient consulted our clinic first in 1991 because of a reduction in visual acuity due to a tumor of the optic nerve head in the left eye. Visual acuity was 1.0 in the right eye and 0.2 in the left eye. Slit lamp examination and intraocular pressure were regular in both eyes. Kinetic perimetry showed a enlarged blind spot besides regular isopters. Funduscopy revealed a pigmented, ill-defined prominence of the optic nerve head with a mossy surface. In annual examinations were found a slowly progredient reduction in visual acuity up to 0.04 durning the last visit in January 2000 as well as a enlargement of the blind spot due to an increasing prominence and pigmentation of the optic nerve head. Because of the clincal aspect, the slowly progressive course, the enlargement of the blind spot with deterioration of vision and especially the florescein angiography, which revealed peripapillary capillary alterations with leakage, we diagnosed a proliferation of the juxtapapillary retinal pigment epithelium. Conclusion: The proliferation of the juxtapapillary retinal pigment epithelium can be differentiated from other pigmented tumors of the optic nerve head by its typical clinical aspect and course and especially by using flourescein angiography.     

视神经挫伤后的眼底血管造影

目的：用荧光素眼底血管造影（Fundus fluorescein angiography,FFA)和吲哚青绿血管造影（Indocyanine green angiography,IGGA)探讨视神经挫伤后，视神经及周围视网膜，脉络膜的循环改变。方法：对30例（30只眼）不同程度的眼球挫伤致视神经损伤的患者进行FFA与ICGA同步检查，并对它们的图像进行分析（本组除外脉络膜破裂）。结果：除1例视盘及周围视网膜，脉络膜荧光大致正常外，其余29例均出现了异常的荧光表现。FFA主要表现为：在造影早期视盘呈象限性或全视盘性的荧光充盈不良，后期荧光素渗漏或始终不能充盈，ICGA主要表现为：在FFA显示的视盘象限性弱荧光区的相邻区域脉络膜充盈时间明显延迟；FFA显示的全视盘性的弱荧光，盘周的脉络膜充盈时间明显延长，在局限性脉络膜灌注不良的对应区均出现了视网膜色素上皮（Retinal pigment epithelium,RPE)的损害，而盘周脉络膜灌注不良的区域，有9例相应区视网膜并未出现RPE的损害；有2例合并视网膜分支动脉阻塞；有19例视盘缺血的部分正是“分水区”的位置，占63.3%，本组病例中有80%视力在0.1以下。结论：眼球挫伤不仅可使视神经损伤，其周围的视网膜，脉络膜均可受到损害，应尽早施行FFA与ICGA检查，它可以详细观察，正确判断视神经挫伤后的视盘缺血情况及周围视网膜，脉络膜损害的范围和程度，及时正确地指导治疗。     

Iris pigment epithelial cells transplanted into the vitreous accumulate at the optic nerve head

BACKGROUND: Iris pigment epithelial (IPE) cells have mainly been investigated in the past for their proposed potential to rescue or even replace degenerated retinal pigment epithelial (RPE) cells after subretinal transplantation in patients with age-related macular degeneration (AMD). More recent reports have characterised the IPE cell as a potent source of trophic factors and cytokines. In our study we investigated the spatial distribution of IPE cells that were injected into the vitreous instead of being injected subretinally. METHODS: IPE cells from Long Evans rats were isolated and injected into the vitreous cavity of Wistar rats without preculturing. Free melanin granules were injected into the vitreous in the same manner. After a period of 2 months, eyes were prepared for histological analysis. Localisation of the injected IPE cells was defined by topographical mapping of the analysed sections. RESULTS: PVR was not observed in any eye. In 8 of 10 injected eyes, IPE cells had accumulated in the prepapillary region. In 2 of 10 eyes, no IPE cells could be detected. The injected melanin granules also accumulated at the optic nerve head, indicating that this is most likely a passive process. In sections of the papillary region containing retinal vessels, the IPE cells seemed to have migrated into the superficial tissue of the optic nerve head. CONCLUSION: Our results demonstrate a way to access the optic nerve head easily and securely without the danger of damaging its fragile structure. This could have important implications for new therapeutic strategies in ocular neurodegenerative diseases like glaucoma. New prospects in gene therapy will require further characterisation of the potential of the IPE cell to produce neuroprotective trophic factors at the optic nerve head.