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Rubeosis iridis and neovascular glaucoma: I. Etiopathogenesis and treatment--the present state of the problem.

Rubeosis iridis is one of the severest complications of the occlusive diseases of retinal vessels associated with retinal hypoxia. In the pathogenesis of rubeosis, the author emphasizes the chronicity of retinal hypoxia which leads to the production of the vasoproliferative substance. This so-called vasoproliferative factor then induces the new formation of vessels on the retina, the optic disc, the iris and the anterior chamber angle. Neovascularization of the anterior chamber angle then very often results in the development of the prognostically very unfavourable neovascular glaucoma. It shows that the most effective methods of treatment of rubeosis iridis are the so-called coagulation techniques-panretinal photocoagulation or cryocoagulation. By application of these techniques, we achieve the destruction of the anatomical substrate which is responsible for the production of the vasoproliferative substance, and the result is involution of rubeosis on the iris and in the anterior chamber angle.

Glaucoma, Neovascular↗

Sildenafil induces retinal vasodilatation in healthy subjects.

BACKGROUND: The cardiovascular effects of sildenafil (Viagra), a selective inhibitor of phosphodiesterase type 5 (PDE5), have been extensively studied. However, its effect on human retinal arteries and veins has not yet been investigated. The effect of a single dose administration of sildenafil on the retinal vessel diameters of healthy subjects was evaluated. METHODS: Sildenafil 50 mg was administered to 10 healthy subjects (male:female = 4:6; mean age 31 (SD 6) years). The diameters of retinal arteries and veins were measured by means of a retinal vessel analyser (RVA) immediately before and at 30, 60, 90, and 120 minutes after sildenafil uptake. Blood pressure, heart rate, and intraocular pressure were monitored in parallel. RESULTS: A significant increase of 5.8% (p<0.001) in both retinal arterial and venous diameters was found 30 minutes after sildenafil uptake. The diameters returned to baseline after 120 minutes. A mild systemic hypotensive response was seen. Changes in heart rate and intraocular pressure were not observed. CONCLUSION: Sildenafil causes a significant dilatation of retinal arteries and veins in healthy subjects. A possible role for PDE5 in the regulation of retinal blood flow is implicated.

Adult↗

[A case of facioscapulohumeral muscular dystrophy with sensorineural hearing loss and retinal angioma].

We report a sporadic case of 12 years old boy with facioscapulohumeral dystrophy (FSHD), sensorineural hearing loss and exudative angioma of bilateral retina. His hearing loss was noted at 9 years, followed by muscle weakness of his right upper extremity at 11 years. Complete neurological examination at 12 years revealed FSH type distribution of muscle weakness with high serum CK level (330 U/L), moderate sensorineural hearing loss and exudative angiomas of bilateral retina. The biopsy from biceps brachii muscle showed advanced dystrophic changes with a dense inflammatory cell infiltration predominating on perivascular distribution and type II fiber predominance. The features of infiltrating lymphocytic surface antigen seen in this case were compatible with those of FSHD rather than those of polymyositis. In the literature, the association of FSHD with hearing loss and retinal vessel abnormalities has been documented on 15 cases as an unusual form of FSHD. However, it has otherwise been noted that the associations of FSHD and hearing loss or retinal vessel abnormalities are unequivocally frequent, Whenever special attention has been made. Morphological examination with light and electron microscopies on the muscle specimen in this patient did not demonstrate any recognizable abnormality such as arterio-venous shunt or thickening of vessel wall basal lamina. However, it cannot be completely excluded that exudation around the abnormal vessel wall in the muscle may play an initial role in the pathogenesis of FSHD. Further morphological survey on vessel abnormalities may be necessary in the FSHD muscle.

Child↗

[Effect of pan-retinal photocoagulation in iris neovascularization].

The authors were able to produce experimental rubeosis iridis in the rhesus monkey's eye on 5 days following occlusion of the major retinal vessels and persistent ocular hypotony. Histopathological examination revealed true neovascularization. This experiment attempted to see whether laser pan-retinal photocoagulation plays an inhibiting effect on the occurrence of rubeosis iridis or not. We first performed laser pan-retinal photocoagulation, and at the same time performed occlusion of the major retinal vessels and persistent hypotony to aid for rubeosis iridis. Clinically, rubeosis iridis appeared within 5 days. At 14 days, histological examination revealed vessels on the surface of the iris following pan-retinal photocoagulation treatment were covered by fibroblast and melanocyte, and their endothelial cells showed no fenestrations. This means that clinical rubeosis iridis is not true neovascularization, but dilatation of the iris vessels. Thus, it was confirmed that pan-retinal photocoagulation inhibits development of iris neovascularization.

Animals↗

Hypothesis: vasoconstriction contributes to amaurosis fugax.

Platelets play a critical role in the pathophysiology of amaurosis fugax. Emboli to retinal vessels apparently produce amaurosis but, in addition, we propose that augmented vasoconstrictor responses and vasospasm may contribute to amaurosis. In this study we tested the hypothesis that constrictor responses of retinal vessels to serotonin, which is released when platelets aggregate, are potentiated in experimental atherosclerosis. Blood flow to the retina was measured in normal and atherosclerotic cynomolgus monkeys. In normal monkeys, infusion of serotonin did not alter flow to the retina. In atherosclerotic monkeys, infusion of serotonin reduced retinal blood flow (in milliliters per minute per 100 g) from 66 +/- 7 (mean +/- SE) to 5 +/- 2. Infusion of serotonin in atherosclerotic monkeys abolished the retinal response to light. Thus, atherosclerosis greatly potentiates constrictor responses to serotonin in the retinal circulation and produces a profound but reversible impairment of retinal function. We propose that altered responses to vasoactive substances that are released by platelets may contribute to the pathogenesis of amaurosis fugax.

Animals↗

Diffuse luminance flicker increases blood flow in major retinal arteries and veins.

It has been shown that diffuse luminance flicker increases optic nerve head blood flow. The current study has been performed to quantify changes in retinal blood flow during flicker stimulation. In a group of 11 healthy volunteers, red blood cell velocity and retinal vessel diameters were assessed with bi-directional laser Doppler velocimetry and the Zeiss retinal vessel analyzer before, during and after stimulation with diffuse luminance flicker. Retinal blood flow was calculated for each condition. Flicker stimulation increased retinal blood flow by +59 +/- 20% (p<0.01) in arteries and by +53 +/- 25% (p<0.01) in retinal veins. These results demonstrate that diffuse luminance flicker increases retinal blood flow in the human retina.

Adult↗

Threshold and retreatment parameters of NPe6 photodynamic therapy in retinal and choroidal vessels.

BACKGROUND AND OBJECTIVE: To determine the threshold fluence for producing choroidal and retinal vascular occlusion with mono-L-aspartyl chlorin e6 (NPe6) photodynamic therapy (PDT) during primary treatment and the effect of retreatment. METHODS: Primary treatment: Rats, rabbits, and monkeys underwent NPe6 PDT to determine the threshold fluences for choroidal and retinal vessel occlusion. The threshold was determined by analyzing fluorescein angiograms for areas of nonperfusion. Retreatment: Dutch-belted rabbits underwent NPe6 PDT followed by fluorescein angiography. Rabbits were retreated one week later at the same parameters. RESULTS: Fluence levels and vascular damage thresholds were always higher for retinal than for choroidal vascular occlusion. Retreatment caused choroidal vessel closure at all tested fluences but retinal capillaries closed only at a fluence > 17.7 J/cm2. CONCLUSION: NPe6 PDT has a lower threshold to occlude choroidal vessels than retinal vessels. The cumulative effect of retreatment does not damage retinal vessels unless the threshold is exceeded during a single retreatment session.

Animals↗

Blood circulation and fluid dynamics in the eye.

The nutrition of the intraocular tissues is accomplished by the retinal vessels, the uveal vessels, and by the aqueous humor. Both morphologically and physiologically the retinal vessels are similar to those in the brain. The endothelial cells of the capillaries are attached to each other by tight junctions, the resistance vessels respond poorly to a large number of drugs, and the blood flow through the retina is autoregulated and very little affected by the sympathetic nervous system. The blood vessels of the iris also have morphological and permeability characteristics similar to those in the brain but they are under a strong influence from the sympathetic nerves and react to many drugs. The blood flow is autoregulated. The blood vessels of the choroid and the ciliary processes are similar to those in the small intestine and in the kidney. The endothelial cells of the capillaries are fenestrated; the vessels respond to sympathetic nervous stimulation and to a large number of vasoactive drugs. Autoregulation of the blood flow is intermediate in the ciliary body and very poor or absent in the choroid...

Animals↗

Incontinentia pigmenti (Bloch-Sulzberger-syndrome): case report and differential diagnosisto related dermato-ocular syndromes.

BACKGROUND: Incontinentia pigmenti (IP; Bloch-Sulzberger syndrome) is an inherited disorder of skin pigmentation that is associated with skin (100%), dental (90%), skeletal (40%), central nervous (40%) and ocular (35%) abnormalities. The pathogenesis is not yet known. The disease is usually seen in females, as it is an X-linked dominantly inherited disease which is lethal in males. PATIENT PRESENTATION: We present a 9-year-old girl with the classical general and ocular signs of IP. She presented in early childhood with inflammatory vesicular skin changes which changed into pigmented skin alterations especially on the trunk. Ocular findings were microphthalmia and retrolental mass formation in one eye and retinal pigmentary changes in the other. In our patient, the spontaneous mutation may have been caused by the family's close neighbourhood to Semipalatinsk, Kasachstan, where regular nuclear tests took place very shortly before the pregnancy with our patient began. DISCUSSION: Ocular involvement is described in about a third of persons affected with IP. A nearly consistent and pathognomonic finding is a pigment retinopathy (mottled diffuse hypopigmentations). A further consistent finding are abnormalities of peripheral retinal vessels with areas of non-perfusion in the outer retina. The retinal pigment epitheliopathy and the abnormalities of retinal vessels are thought to be the underlying pathognomonic findings, with all other ocular signs being secondary (cataract, leucocoria, optic atrophy, strabismus, nystagmus and microphthalmus). Exudative retinal detachment occurs only in a minority, usually in very early childhood, when the skin lesions are exudative as well. IP patients should, however, be clinically observed regularly because of their retinal pigmentary changes.

Abnormalities, Multiple↗

Multicenter clinical experience using an erbium:YAG laser for vitreoretinal surgery.

PURPOSE: To evaluate the advantages, disadvantages, safety, complications, and surgical applicability of an erbium:YAG laser system for maneuvers in vitreoretinal surgery. METHODS: A prospective, consecutive trial of 68 eyes in 66 patients undergoing vitreoretinal surgery in which an erbium:YAG laser with graduated output from 0.2 to 5.0 mJ per pulse, repetition rate of 2 to 30 Hz, and equipped with a flexible fiber optic and interchangeable 20-gauge intraocular fiber optic endoprobes was used to perform specific maneuvers, including transection, incision, and ablation of membranes, retinotomy, vessel coagulation, iridectomy, and lens tissue ablation. The patients were treated in five centers in contemporary vitreoretinal surgical settings for surgical indications, including proliferative diabetic retinopathy, proliferative vitreoretinopathy, epiretinal membrane, and retinopathy of prematurity. RESULTS: One hundred seventy-four maneuvers were performed with an overall surgical efficacy rating of excellent or good in 84% of maneuvers, ranging from a high of 100% for subretinal membrane transection to a low of 25% for coagulation of blood vessels. Complications included retinal break or photocoagulative injury in 5% of epiretinal membrane incisions, minor bleeding from transected retinal vessels during 29% of retinotomies, and intraocular lens damage during two posterior capsulotomies. The most significant limitation was the cautious pace used during maneuvers near the retinal surface. CONCLUSION: The erbium:YAG laser is capable of versatile new approaches offering precise tissue cutting and ablation in vitreoretinal surgical maneuvers with a high degree of safety. The main limitation encountered was the slow speed of certain critical maneuvers near the retina.

Adult↗

Comparisons between microvascular changes in cerebral and non-cerebral malaria in mice, using the retinal whole-mount technique.

CBA/T6 mice inoculated with Plasmodium berghei ANKA strain (PbA) exhibited cerebral symptoms and died from cerebral malaria 6-8 days p.i. whereas DBA/2J mice developed (around days 6-9) a non-fatal cerebral malaria, with milder cerebral symptoms, and died between days 15 and 22 from other malaria-related complications. When inoculated with P. berghei K173 (Pb) these mouse strains did not develop cerebral malaria. These mouse/parasite strain combinations were used, in conjunction with the retinal whole-mount technique, to elucidate factors critical in the pathology of murine cerebral malaria. CBA/T6 mice infected with PbA (PbA-CBA mice) demonstrated mild changes in vascular permeability as early as days 2-3, prior to the appearance on day 5 of cerebral symptoms, whereas mice with non-cerebral malaria did not show any vascular permeability changes until the very late stage of the disease (days 14-22). In the PbA infections, progressive deterioration of endothelial barrier properties, demonstrated by Evans' Blue leakage both generally and from specific focal areas, as well as a developing monocytosis and adherence of mononuclear cells to the endothelium of the retinal vessels continued until death (in CBA/T6 mice) or resolution (in DBA/2J mice). Adherent monocytes, particularly in PbA-CBA mice, were associated with reduced Hoechst staining of individual endothelial cells and a banking up proximally of both parasitized and non-parasitized blood cells in the small blood vessels, often with accompanying focal leakage of Evans' Blue from the retinal vessels. The occurrence and severity of these early changes in the microcirculation correlated with the subsequent development of cerebral symptoms. Monocyte margination appeared to be the most significant factor associated with the development of cerebral symptoms.

Animals↗

Immunolocalisation of the VEGF receptors FLT-1, KDR, and FLT-4 in diabetic retinopathy.

AIM: To determine the spatial and temporal changes in the staining pattern of the VEGF receptors FLT-1, KDR, and the putative receptor FLT-4 during the pathogenesis of diabetic retinopathy. METHODS: Immunohistochemical localisation of VEGF receptors, using antibodies against FLT-1, FLT-4, and KDR, was carried out on specimens of normal human retina (n = 10), diabetic retinas (a) with no overt retinopathy (n = 12), (b) with intraretinal vascular abnormalities but no proliferative retinopathy (n = 5), (c) with active proliferative retinopathy (n = 6), and (d) with no residual proliferative retinopathy after scatter photocoagulation therapy (n = 14), and surgically excised diabetic fibrovascular membranes (n = 11). The degree and pattern of immunostaining was recorded. RESULTS: FLT-1 staining was apparent in the retinas from both non-diabetic and diabetic retinas; weak to moderate staining was generally confined to the inner nuclear layer, the ganglion cell layer, and the retinal vessels during all stages of the disease process. Staining of the retinal vessels was raised in diabetic tissue compared with non-diabetic tissue. The preretinal vessels of the diabetic subjects stained moderately to intensely for FLT-1. In contrast with FLT-1 staining minimal immunostaining for KDR was demonstrated in the non-diabetic eyes and the unlasered eyes; however, weak staining for KDR was observed in the inner nuclear layer and the ganglion cell layer of the unlasered eyes with diabetic changes. In those retinas with preretinal neovascularisation KDR immunoreactivity was moderate to intense in the intra- and preretinal vessels. However, in the excised membranes, where the vessels may have been in a quiescent state, the levels of KDR were weak to moderate. After apparently successful laser treatment KDR staining was reduced in the intraretinal vessels. Minimal FLT-4 staining was observed throughout normal eyes while weak to moderate FLT-4 staining was generally confined to the inner nuclear layer and the ganglion cell layer of the unlasered diabetic eyes. Weak to moderate levels of FLT-4 staining were observed in the intraretinal vessels except after apparently successful laser treatment where reduced levels of staining were observed. Weak to moderate staining was observed in the preretinal vessels. CONCLUSIONS: This study supports a role for FLT-1, KDR, and possibly FLT-4 in the pathogenesis of diabetic retinopathy; however, their specific roles in the progression of the disease may differ.

Aged↗

[Observation of retinal vasculature in experimental renal hypertension rat using bis-benzimide].

The retinal vessels of experimental renal hypertensive rats (RHRS), spontaneously hypertensive rats (SHRS), and normotensive Wistar-Kyoto rats (WKYS) were studied using bis-benzimide vital staining. In the bis-benzimide stained flat retinal preparations (B-FRP) of SHRS, it was only observed that the endothelial nuclei were elongated and their arrangement was irregular. In B-FRPS of RHRS, the arrangement was more irregular and the nuclei disappeared at the point where the caliber irregularity was marked. The nuclei of smooth muscle cells, which were arranged circumferentially, and the perivascular tissues were clearly identified. This finding suggests that hyperpermeability or disruption of the blood-retinal barrier did not occur in the mild hypertension but in the severe hypertension. The retinal vessels of RHRS in the regressive stage also showed seved the same kinds of findings in electron microscopy.

Animals↗

Histopathology of bone spicule pigmentation in retinitis pigmentosa.

PURPOSE: To evaluate bone spicule pigmentation, a fundus feature in retinitis pigmentosa (RP) formed by migration of pigment-containing cells to perivascular sites in the inner retina. METHODS: The authors performed light and electron microscopy, including immunocytochemistry, on the retinas from ten patients with RP and five normal donors. RESULTS: The pigment-containing cells in regions of bone spicule pigmentation were derived from the retinal pigment epithelium (RPE). The translocated cells were remarkably polarized with a number of specializations characteristic of RPE cells in situ, but they did not contain lipofuscin granules and were not immunoreactive for cellular retinaldehyde-binding protein. The cells were linked by junctional complexes and formed epithelial layers around retinal vessels and next to the inner limiting membrane. Adjacent Müller cell processes contained glial fibrillary acidic protein-positive filaments and formed microvilli and intermediate junctions, resembling those in the external limiting membrane. Vascular endothelial cells adjacent to the translocated RPE cells were thin and fenestrated, resembling the choriocapillaris, and were separated from the pigmented cells by a layer of extracellular matrix similar in organization to Bruch membrane. Thickening of the matrix layer caused narrowing and occlusion of the vascular lumina. CONCLUSIONS: The lack of lipofuscin granules and cellular retinaldehyde-binding protein immunoreactivity in the translocated RPE cells is probably related to the loss of photoreceptors. The development of fenestrations in the endothelial cells correlates with the leakiness of retinal vessels to fluorescein observed in some cases of RP. Narrowing and occlusion of vascular lumina by thickening of the surrounding layer of extracellular matrix may contribute to the loss of inner retinal neurons found in RP. These changes in the RPE, blood vessels, glia, and inner neurons warrant consideration in designing therapies to restore vision to degenerate retinas.

Adult↗

Histopathology of Goldmann-Favre syndrome obtained by full-thickness eye-wall biopsy.

The first histopathologic specimen form the eye of a patient with Goldmann-Favre syndrome was obtained by full-thickness eye-wall biopsy. Diagnosis was established by an early history of night blindness, characteristic clinical features including atypical pigmentary retinopathy, peripheral retinoschisis, opaque "sclerotic-appearing" peripheral retinal vessels, vitreous changes including liquefaction and condensed vitreous bands and a non-detectable electroretinogram (ERG). Histopathologic changes from a 4 mm peripheral area included diffuse degenerative changes involving predominantly the sensory retinal layers with a relatively normal pigment epithelium and choroid. Vascular changes included thickened retinal vessel basement membranes and areas of vascular occlusion. These findings are compatible with a primary photoreceptor involvement in addition to a vascular component. A thick preretinal membrane of glial tissue was an additional finding.

Adult↗

Mucolipidosis I.

A case of mucolipidosis I had clinical and histopathologic features that were a combination of changes found in both mucopolysaccharidoses and sphingolipidoses. Corneal clouding, spokelike cataracts, tortuous conjunctival and retinal vessels, and strabismus were clinical findings. Histopathologically, there were inclusion vacuoles similar to those seen in mucopolysaccharidoses; lamellar bodies typical of sphingolipidoses were rare. These vacuoles were seen in conjunctival and corneal epithelium and fibrocytes, conjunctival and retinal vessel endothelium, and all retinal cell layers.

Conjunctiva↗

Identification of glaucomatous visual field defects from examination of monocular photographs of the optic disc.

A study was carried out of monocular disc photographs from 33 eyes for which the visual fields on both static profile and kinetic perimetry has been performed. Physical signs looked for at the optic disc included thinning of the neuroretinal rim, angulation of retinal vessels, extension of laminar dots, undercutting of the neuroretinal rim, and absence and pallor of the neuroretinal rim. These signs together proved more accurate than kinetic Goldmann perimetry in identifying the presence of glaucomatous visual field defect. Of these signs angulation of the retinal vessels was the one most consistently present.

Glaucoma↗

Scanning laser ophthalmoscope imaging of fluorescein-labelled blood cells.

PURPOSE: To demonstrate the feasibility of a technique for the visualization by scanning laser ophthalmoscope (SLO) of fluorescein-labelled autologous leukocytes and platelets in retinal vessels. METHOD: Individual blood samples from rats and rabbits were centrifuged to isolate platelets and leukocytes, then passively labelled with fluorescein and reinjected into the same animal. An SLO was used to visualize and record cell displacement in the retinal circulation. Labelled platelets were analysed by flow cytometry. RESULTS: By SLO, platelets appeared as a heterogeneous particle flow, and individual leukocytes appearing as brighter spots could easily be traced. Flow cytometry showed that after labelling platelets were well individualized and their size was slightly increased. CONCLUSION: Circulating blood cells can be visualized in retinal vessels by a simple method consisting of passive labelling of autologous platelets and leukocytes by fluorescein. No platelet toxicity was detected. This method could be applied to the study of blood cell movement in human retinal vascular diseases.

Animals↗