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Relation of pre-LASIK and post-LASIK retinal lesions and retinal examination for LASIK eyes.

AIMS: Analysis of highly myopic eyes (mean myopia -11 D) with post-LASIK vitreoretinal complications (breaks, retinal detachment) that also had pre-LASIK vitreoretinal pathology (lattice, breaks). METHODS: Retrospective case series. RESULTS: 67 eyes in 56 patients with pre-LASIK retinal examination developed post-LASIK vitreoretinal complications. 17 of the 67 eyes (25.4%) had pre-LASIK vitreoretinal pathology. 10 of the 17 eyes that underwent pre-LASIK prophylactic retinal treatment still developed post-LASIK lesions. They developed adjacent to pre-LASIK lesions for 15 of 17 eyes (88.2%), and outside of quadrant(s) of pre-LASIK lesions for five eyes (29.4%). CONCLUSION: Pre-LASIK retinal examination may predict locations of certain post-LASIK retinal lesions that may develop in highly myopic eyes with pre-LASIK vitreoretinal pathology, but prophylactic treatment may not prevent all post-LASIK vitreoretinal complications.

Adult↗

Numbers of axons in the optic nerve and of retinal ganglion cells during development in the marsupial Setonix brachyurus.

Numbers of axons during postnatal development in the optic nerve of the marsupial Setonix brachyurus were estimated from electron micrographs. Between 14 and 45 days axon totals rose 10-fold from 95,000 to 961,000. Thereafter, counts decreased gradually by almost 5-fold stabilising at the adult level of 180,000-224,000 between 130-150 days. Myelinated axons were first seen at 85 days and constituted 76% of all axons by 150 days, compared to almost 100% in the adult. At comparable stages of development, estimates of cell number in the ganglion cell layer were made from sectioned and whole-mounted retinae. Ganglion cells, labelled with horseradish peroxidase (HRP) injected into the optic tract and visual brain centres, reached a maximum of 304,000 by 50 days. This value was only one-third higher than the adult ganglion cell estimate of 202,000, to which counts fell by 70 days. Such a fall of ca. 100,000 ganglion cells was matched by a reduction from 443,000 to 361,000 in the total number of cells in the retinal ganglion cell layer, that is, cells labelled by HRP plus those which remained unlabelled. Thus, during development axon counts exceeded adult values 4-fold whereas ganglion cell totals were only one-third higher than the mature value. The shortfall of ganglion cells to optic axons indicates that during development the transiently high axon number cannot be explained by a correspondingly raised count of ganglion cells. It is therefore necessary to hypothesise a substantial fibre population which temporarily projects into the nerve from either the brain or the opposite eye. Alternatively, optic axons may branch extensively during development with subsequent loss of collaterals.

Age Factors↗

Rhegmatogenous retinal detachment associated with branch vein occlusion.

Proposed mechanisms for rhegmatogenous retinal detachment after branch retinal vein occlusion (BRVO) include hole development from preexisting retinal cysts and vitreoretinal traction secondary to retinal neovascularization. Damage caused by choriocapillary obstruction may also occur in some of the retinal breaks. Vitreoretinal traction without associated retinal neovascularization has not been previously emphasized as a pathogenetic mechanism. We document both iatrogenic and idiopathic vitreoretinal traction as causes of rhegmatogenous retinal detachment in ischemic retina after BRVO. A literature review of the role of retinal traction with and without associated neovascularization in the development of retinal tears after BRVO is included.

Aged↗

Effect of monocular blockade of retinal activity on the development of visual callosal connections in the rat.

It has been previously reported that neonatal monocular enucleation in rats and hamsters induces the development of an anomalous band of callosal connections in the middle of area 17 (primary visual cortex) in the hemisphere ipsilateral to the remaining eye. In order to determine whether this effect is due to elimination of retinal activity in one eye, we used the anatomical tracer horseradish peroxidase (HRP) to study the pattern of visual callosal connections in rats in which retinal activity had been blocked by intraocular injections of tetrodotoxin during the first two weeks of life. We found that the callosal pattern in the hemisphere ipsilateral to the eye not treated with tetrodotoxin was not distinguishable from the pattern present in normal rats. In particular, we did not observe the anomalous extra band of callosal connections that occurs in area 17 in the hemisphere ipsilateral to the remaining eye in monocularly enucleated rats. These results indicate that blockade of retinal activity in one eye is not sufficient to cause the marked changes in the pattern of visual callosal connections that are induced by neonatal monocular enucleation.

Animals↗

Retinopathy of Great Pyrenees dogs: fluorescein angiography, light microscopy and transmitting and scanning electron microscopy.

OBJECTIVE: Investigation of the pathogenesis of Great Pyrenees retinopathy. ANIMALS: One male and two female puppies of parents who were affected with Great Pyrenees retinopathy and one 4-year-old affected adult male Great Pyrenees dog. PROCEDURE: The puppies were examined daily from 7 weeks of age by indirect ophthalmoscopy and their fundi were photographed until the lesions were static. Fluorescein angiography was completed at 7 weeks of age, within 24 h of detection of ophthalmoscopic lesions, and then weekly. The eyes of a 4-year-old and two 20-week-old puppies were examined with light microscopy, and transmitting and scanning electron microscopy. RESULTS: Blocked choroidal fluorescence was detected at 7 weeks of age. The blocked fluorescence enlarged, when the characteristic serous retinal detachments developed at 11 weeks of age. The detachments enlarged in size and number until the puppies were approximately 20 weeks old. Fluorescein pooling confirmed the presence of transient retinal pigment epithelial detachments. Leakage of dye into serous retinal detachments was not detected in this study. Light microscopy and transmitting and scanning electron microscopy confirmed the presence of multifocal serous retinal detachments with focal retinal degeneration that extended to the inner nuclear layer in a 4-year-old dog. The retinal detachments were accompanied by hypertrophy, hyperplasia, increased pigmentation, and vacuolation of the retinal pigment epithelium. CONCLUSIONS AND CLINICAL RELEVANCE: Great Pyrenees retinopathy is manifested by multifocal serous retinal and retinal pigment epithelial detachments. These detachments are similar to those noted with central serous retinopathy of humans. The sudden development of multifocal retinal and retinal pigment epithelial detachments, and the serous nature of these detachments, supports a theory that they develop secondary to focal secretion and absorption defects in retinal pigment epithelial cells. Given the age of the puppies when the blocked choroidal fluorescence was noted and maturation of the dog retina at 8 weeks postpartum, this retinopathy is considered to be a retinal pigment epithelial dysplasia. This unique inherited retinopathy offers an opportunity to study retinal pigment epithelial secretion.

Animals↗

[Follow-up of HIV infected patients with reduced pattern ERG].

We have recently reported a reduction of pattern electroretinogram (p-ERG) in patients with HIV infection. Amplitudes were reduced in HIV-infected patients with microangiopathy, but also in some cases with normal fundus. These findings suggested the existence of diffuse defects in ganglionic cell activity in HIV-infected patients. We have now started a prospective follow-up study in order to pursue the development of (a) p-ERG amplitudes and (b) funduscopic changes and visual acuity in these patients. In patients with normal fundus or microangiopathy who did not develop cytomegalovirus (CMV) retinitis, no significant tendency for the p-ERG amplitudes to fall could be demonstrated during the observation period of 1-16 (mean: 7) months. With the appearance of retinitis, the p-ERG amplitude decayed. In some cases, a pathologic p-ERG was recorded before retinitis appeared: 3 of 12 patients with p-ERG amplitudes in the pathological range later developed CMV retinitis and only 1 of 21 patients with normal p-ERG later developed retinitis. In some patients with AIDS or related disorders, p-ERG may be a useful additional diagnostic tool.

Adult↗

Localised gamma irradiation and experimental intraocular proliferation.

A controlled study was undertaken to assess the effect of gamma irradiation on post-traumatic intraocular cellular proliferation. A standard perforating injury in the posterior segment of the rabbit eye was used to induce intraocular cellular proliferation and vitreo-retinal membrane formation. The site of injury was irradiated with an ophthalmic Cobalt60 applicator which provided a continuous source of gamma rays. Non-irradiated eyes developed traction retinal detachments associated with post-traumatic vitreo-retinal membranes. Irradiated eyes developed attenuated membranes or atrophic retinal scars, with the retina remaining attached. The membranes in non-irradiated eyes were highly cellular with abundant collagen, while irradiated membranes had fewer cells within a sparse collagen matrix. The episcleral fibroblasts, on autoradiographic studies appeared to be the main source of the cells that formed the proliferating tissue in both non-irradiated and irradiated eyes. In irradiated eyes both the inflammatory response and division of fibroblasts were delayed and reduced.

Animals↗

Cytomegalovirus esophagitis in AIDS: a prospective evaluation of clinical response to ganciclovir therapy, relapse rate, and long-term outcome.

PURPOSE: Although cytomegalovirus (CMV) esophagitis is an important complication of acquired immunodeficiency syndrome, there has been little study specifically addressing the response to currently available antiviral therapy, relapse rate without maintenance therapy, and long-term outcome. PATIENTS AND METHODS: Over a 45-month period, 44 patients with CMV esophagitis established endoscopically and histopathologically were prospectively identified from among all human immunodeficiency virus (HIV)-infected patients undergoing endoscopy. Induction therapy consisted of intravenous ganciclovir at 10 mg/kg per day for approximately 14 days. Foscarnet was given at 60 mg/kg every 8 hours for nonresponders to ganciclovir. RESULTS: Of these patients, 35 completed induction ganciclovir therapy, resulting in a complete response in 17 (49%) and a partial response in 10 (29%), yielding a 77% overall response rate. Seven of 8 nonresponders were subsequently treated with foscarnet, with a clinical response seen in 5 patients. In the 18 eventual complete responders to ganciclovir or foscarnet followed up without maintenance therapy, 7 (39%) relapsed at a median of 4 months (range 2 to 18 months). In all cases, relapse was manifested by recurrent odynophagia. Reinduction ganciclovir therapy yielded a complete response in 1 patient and a partial response in 2, and induction foscarnet treatment resulted in a complete response in the other treated patients. During long-term follow-up, 1 complete responder developed CMV colitis with concurrent retinitis, and 4 other patients developed retinitis. The median survival after diagnosis was 8.2 months, although survival for greater than 1 year was seen in 4 patients. No patient died as a direct result of esophageal disease, although ulcer-related bleeding may have contributed to death in 2 patients with end-stage liver diseases and hepatic encephalopathy. CONCLUSIONS: CMV esophagitis has a favorable response to induction ganciclovir therapy, and a long-term remission may occur after induction therapy alone. Despite the favorable response to ganciclovir therapy, the long-term survival is poor, reflecting the severe immunodeficiency of these patients.

AIDS-Related Opportunistic Infections↗

Dexamethasone reduces oxygen induced retinopathy in a mouse model.

Dexamethasone is widely used in the postnatal period. Its impact on retinopathy of prematurity (ROP) is extremely controversial; published studies have found a detrimental, protective, or no effect on ROP. The goal of this study was to test the hypothesis that use of dexamethasone during the injury phase (oxygen exposure) reduces the severity of oxygen-induced retinopathy (OIR) in a mouse model. C57BL6 mice pups were exposed to either room air or hyperoxia (75% FiO2) from postnatal d 7 through 12 (PN7-12) with or without dexamethasone (0.5 mg/kg/d s.c.) and killed on PN17-21. Retinopathy was assessed by a scoring system of retinal flat mount preparations and periodic acid-Schiff (PAS) staining of retinal sections. Pups exposed to dexamethasone and oxygen had a lower median retinopathy score of 5 (4, 6) [median (25th, 75th quartile)] compared with animals exposed to oxygen alone with median score of 9 (6, 10) with p < 0.001. PAS staining for extra retinal neovascularization in the dexamethasone and oxygen treated animals showed a significant reduction in number of nuclei extending beyond the inner limiting membrane when compared with oxygen exposed alone (p = 0.04). Animals treated with dexamethasone had decreased weight gain compared with control animals. Dexamethasone did not appear to affect the normal development of retinal vasculature as assessed by the scoring system when compared with control animals. Thus, dexamethasone decreases severity of OIR without having an adverse effect on normal retinal vascular development in the mouse model. We speculate that dexamethasone decreases the injury response that occurs during the hyperoxic phase, thus protecting the developing vasculature and improving the subsequent retinopathy.

Animals↗

Exogenous leukemia inhibitory factor (LIF) attenuates retinal vascularization reducing cell proliferation not apoptosis.

To study the effect of leukemia inhibitory factor (LIF) on rat retinal vascular development, Sprague-Dawley rats at postnatal age 3 days (p3) were given intraperitoneal (IP) LIF and analysis performed at p6 (p3/6). p7 rats were given intravitreous (IV) LIF and analysis performed at p9 (p7/9). Control animals were PBS injected. At the time of analysis retinal flatmounts were prepared and stained with Griffonia lectin and activated caspase-3. The retinal peripheral avascular area was measured and number of apoptotic cells counted. In vitro, human retinal microvascular endothelial cells (RMVECs) were cultured in media containing LIF, with and without neutralizing antibody to LIF. Cells were stained with activated caspase-3 and apoptotic cells counted. Proliferation was measured by counting cell numbers, and cell cycle stage was determined using propidium iodide staining and FACS analysis. LIF injected either IP or IV had no effect on body weight or total retina area, but significantly increased the peripheral retinal avascular area. In both IP and IV injected groups there was no difference in the number of apoptotic cells between PBS- or LIF-injected groups; although in the p7/9 retinas, both injected groups had significantly more apoptotic cells than the non-injected group. In vitro, there was no effect of LIF on RMVEC apoptosis; however, cell counts were significantly lower in the LIF-treated group. Antibody to LIF restored the cell counts to untreated levels. LIF reduced the number of cells in S phase. LIF attenuates retinal vascular development in vivo through growth arrest, and not apoptosis, of endothelial cells.

Animals↗

Familial exudative vitreoretinopathy.

PURPOSE: To evaluate the natural history of Familial Exudative Vitreoretinopathy (FEVR) with emphasis on the effect of the age of onset on its severity and on the development of late complications such as cataract and retinal detachment. Also, to evaluate affected patients for DNA abnormalities. METHODS: The records of thirty-nine patients with FEVR were studied. All were asked to come in for a final follow-up examination. The referring physician was asked to provide the latest findings for those who could not. On 10 patients, karyotypes were prepared. RESULTS: Only 2 of 28 patients whose onset of symptoms was prior to their third birthday had a final visual acuity of 20/200 or better. Older patients had a better prognosis, because they were more likely to have asymmetrical retinal deterioration with only one eye deteriorating. Preservation of good visual acuity into the teens and later was no guarantee that deterioration would not occur. In 3 eyes of 4 patients who were asymptomatic until 15 years of age, the final visual acuity was counting fingers or worse. In 5 patients, retinal detachment developed 6 to 17 years after apparent stabilization. The karyotype of 10 patients showed no evidence for rearrangement, altered size, translocations or deletions of chromosome 11 or any other chromosome. Of the 31 eyes in patients older than 15 years, 10 (32%) had a significant cataract. Three eyes underwent cataract surgery. CONCLUSIONS: The prognosis for infants with FEVR is extremely poor and the long-term prognosis for patients with a later onset of the condition is guarded. Retinal detachment, macular dragging, and cataract are common late complications which can develop even in patients whose eye findings appear to be stable. Karyotype studies ruled out involvement of chromosome 11 or others at a gross level, but did not exclude them at the location for some genetic defect related to FEVR because single base changes and small deletions or insertions may be undetectable by the methods utilized.

Adolescent↗

An instructive role for retinal waves in the development of retinogeniculate connectivity.

A central hypothesis of neural development is that patterned activity drives the refinement of initially imprecise connections. We have examined this hypothesis directly by altering the frequency of spontaneous waves of activity that sweep across the mammalian retina prior to vision. Activity levels were increased in vivo using agents that elevate cAMP. When one eye is made more active, its layer within the LGN is larger despite the other eye having normal levels of activity. Remarkably, when the frequency of retinal waves is increased in both eyes, normally sized layers form. Because relative, rather than absolute, levels of activity between the eyes regulate the amount of LGN territory devoted to each eye, we conclude that activity acts instructively to guide binocular segregation during development.

Animals↗

A case of diabetic retinopathy with both retinal neovascularization and complete posterior vitreous detachment.

PURPOSE: Report of a case with retinal neovascularization developing in the setting of diabetic retinopathy despite complete posterior vitreous detachment (PVD). CASE REPORT: A 76-year-old man had had type II diabetes mellitus for more than 30 years. Weiss' ring was detected by direct and indirect ophthalmoscopy. PVD was thus considered to be complete. On the other hand, fluorescein angiography showed two areas of hyperfluorescence at the margin of the retinal nonperfusion area. CONCLUSIONS: The present case underscores the importance of periodic follow-up using fluorescein angiography, given the probability of retinal neovascularization development and proliferative changes for many years even in diabetic retinopathy associated with complete PVD.

Aged↗

Shifting retinal maps in the development of the lateral geniculate nucleus.

During development, the bilateral projections from each eye to subcortical visual structures in the mammal initially overlap throughout the majority of the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC) before retracting to their separate territories. It has been shown in the ferret that during this period the larger contralateral retinal projection to both the dLGN and SC is retinotopically organised. By making small retinal lesions, and then anterogradely labelling the remaining retinofugal pathway from one eye, this study demonstrates that on the day of birth there is a superficial region of the dLGN in which the retinotopic map cannot be demonstrated. This region may be the presumptive C laminae. Further, by making small lesions in the temporal retina it has been shown that the smaller ipsilateral projection is also retinotopically organised before it retracts. Large lesions confined to the nasal retina had no effect on the pattern of label in the ipsilateral dLGN. Consequently, the ipsilateral projection which fills the nucleus at this stage must arise from the temporal retina. Because of this, the process of segregation requires that the retinotopic maps from each eye shift in relation to one another, and the borders of the nucleus to form the adult pattern.

Animals↗

[Risk factors of pseudophakic detachment].

UNLABELLED: The increase of pseudophakic retinal detachments has raised the question about its risk factors. According to the literature, complicated cataract surgery rarely contributes to pseudophakic retinal detachment. Nevertheless, we noted a high proportion of defects in the capsular barrier among our patients. We therefore reevaluated our charts for perioperative and epidemiologic risk factors for pseudophakic retinal detachment. PATIENTS: Seventy-six patients with pseudophakic retinal detachment after extracapsular cataract operation with intraocular lens implantation were referred to the Ophthalmology Department of Freiburg University between 1986 and 1991. Their case records were analyzed for possible risk factors for retinal detachment. RESULTS: When retinal detachment developed, posterior lens capsule was not intact in 52/76 eyes (68%), the highest rate published so far. In 37 eyes capsular rupture occurred during cataract surgery, in 16 eyes followed by vitreous prolapse and in 9 eyes with persistent vitreous incarceration. Three eyes had vitreous prolapse via zonula. In 10 eyes YAG laser capsulotomy preceded detachment, and in 2 eyes capsular rupture occurred during an aspiration procedure for secondary cataract. The high proportion of intraoperative capsular ruptures is understandable if we assume a 2% risk of intraoperative capsular rupture, followed by a 20-fold increase in retinal detachment. The latency between cataract surgery and retinal detachment was 22 months after uncomplicated surgery, after YAG laser capsulotomy 13.5 and after intraoperative capsular rupture 10 months (medians). CONCLUSION: Vitreal complications in cataract surgery facilitate the development of retinal detachment. The incidence of defect posterior capsules and vitreal complications among patients with pseudophakic retinal detachments can be explained by assuming a 10- to 20-fold increase in retinal detachments after these complications. In cases of capsular or zonular rupture, all means, including prophylactic vitrectomy of vitreal strands, should be used to avoid permanent vitreous traction. However, the rate of retinal detachments after YAG laser capsulotomies only minimally surpassed the rate after uncomplicated cataract surgery. The risk for retinal detachment is not determined so much by the capsular defect itself. It is determined rather by the circumstances in which it occurred and by the grade of vitreal disturbance.

Adult↗

Posterior vitreous detachment and neovascularization in diabetic retinopathy.

The authors evaluated the effect of posterior vitreous detachment (PVD) in 172 eyes (114 patients) with nonproliferative diabetic retinopathy on the development of retinal or optic disc neovascularization. Patients were followed for more than 6 months after the initial vitreous examination (mean, 32 months). None of the patients 39 years of age or younger had PVD, but this condition became more prevalent thereafter with age. In 124 eyes of patients 40 years of age or older, neovascularization developed eventually in 20 (22%) of 93 eyes without PVD but in only 1 (3%) of 29 eyes with complete PVD (P less than 0.05). A vitreous examination was invaluable in predicting the development of retinal or optic disc neovascularization in diabetic patients 40 years of age or older.

Adolescent↗

Differentiation of ganglion cells and amacrine cells in the rat retina: correlation with expression of HuC/D and GAP-43 proteins.

In order to understand the development of retinal cells, we have studied the temporal expression of HuC/D protein in embryonic, postnatal and adult rat retina. During development and in the adult retina, practically all cell somata in the ganglion cell layer and the vast majority of conventional amacrine cells in the inner nuclear layer displayed HuC/D immunoreactivity. Most but not all ganglion cells expressed HuC/D at embryonic day 15, suggesting a delay between final mitosis and the initiation of HuC/D expression. Immunoreactivity for HuC/D was also evident in developing but not mature horizontal cells. Combined immunohistochemical visualization of HuC/D protein and the growth-associated protein (GAP-43) showed a distinct localization of GAP-43 in a specific compartment close to the somato-dendritic region of developing HuC/D-positive cell somata. The localization of GAP-43 immunoreactivity to a specific soma compartment became less evident during maturation. Immunoreactivity for HuC/D and GAP-43 was also discernible in horizontal cells at postnatal day 14. In the adult retina, most GAP-43 immunoreactivity was seen in the inner plexiform layer. Detailed analysis showed that HuC/D and GAP-43 expression is restricted to subsets of retinal neurons during development and in the mature retina. Thus, GAP-43 appears to be correlated with initial steps of differentiation and outgrowth of dendritic processes in HuC/D-positive ganglion and amacrine cells.

Amacrine Cells↗