The natural history of retinal holes with special reference to the development of retinal detachment and the time factor involved.
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Follow-Up Studies↗
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The development of retinitis in mice with nonfatal herpes simplex encephalitis.
A mutant strain of herpes simplex virus, type 1 (HSV1), selected for high resistance to acyclovir (ACV) was inoculated intracerebrally into mice. The mice survived with no obvious neurological signs but developed cataracts within 4-8 weeks of inoculation. Histological examination revealed only a mild encephalitis, but around 7 days after injection a florid, necrotizing, viral retinitis developed. There was almost simultaneous involvement of both eyes. Inflammatory cell infiltration and early myelin degeneration along the course of the optic nerve suggested cell to cell spread of virus to the retinal nerve cell bodies. Although virus could only be recovered from the eye in the early stages of retinitis, destruction of the neural retina was frequently complete and subsequently the optic nerve showed Wallerian type degeneration. Visible cataracts were a late complication, but changes in the lens were initiated during the phase of acute retinitis. This experiment shows that antiviral agents may induce mutant forms which cannot reproduce classical disease, but are capable of permissive infection in unexpected sites. Herpes retinitis is occasionally recognized as a complication of fatal HSV encephalitis in man. Theoretically, more effective treatment of encephalitis with nucleoside analogues, for example with acyclovir, could reveal the development of retinitis in survivors.
Animals↗
Abnormal retinal vascular development in IL-18 knockout mice.
Recent studies have indicated that interleukin 18 (IL-18) might act as either an angiogenic or an angiostatic factor, but the true function of this protein in vascular development is unclear. We therefore investigated the role of IL-18 in the formation of retinal vessels. Development of the retinal vasculature was compared in IL-18 knockout (KO) and wild-type (WT) mice at several different time points. The formation of vessels was evaluated using angiography of flat-mounted retinal samples after inoculation with fluorescein dextran. Retinal samples from both groups were also evaluated through histological examinations, and the expression of angiogenic factors was examined using the reverse-transcription-polymerase chain reaction. The capillary retinal vessels in both WT and IL-18 KO mice had reached the peripheral retina by postnatal day (P) 7. However, IL-18 KO mice showed angiectasis and vascular leakage at P7, especially in the mid-peripheral retina. These symptoms were not observed in WT mice at any stage. Histopathological analysis confirmed abnormal vascular formation in IL-18 KO mice at P14. Interestingly, these abnormalities regressed over time and had disappeared by P84. Several angiogenesis-associated factors, including vascular endothelial growth factor (VEGF), basic fibroblast-growth factor (bFGF), platelet-derived growth factor (PDGF) and pigment epithelium-derived factor (PEDF), were overexpressed in the retinas of IL-18 KO mice compared with those of WT mice at P14. Interferon-gamma was detected only in WT mouse retinas at P14. These results provide new evidence for the role of IL-18 in retinal vascular development.
Angiogenic Proteins↗
Elastase is not required for L-DNase II activation during apoptosis in developing chicken neural retina.
During retinal development, the neuronal death is carried out by the mechanism of apoptosis. Among the different endonucleases activated, L-DNase II seems to be responsible for most of DNA degradation in this tissue. L-DNase II derives from LEI (Leukocyte Elastase Inhibitor) by a post-translational modification carried out by elastase in apoptosis induced in vitro. In this study, we investigated whether elastase could be implicated in apoptosis occurring during retinal development. Although elastase and LEI/elastase complex are colocalized in retinal sections, the LEI/elastase complex, detected by Western blot, does not change at all stages of development. However, at pH 4 retinal extracts show an enhanced activation of the L-DNase II. These results suggest that an acid protease, such as a cathepsin, may be implicated in neuronal retinal apoptosis.
Animals↗
Branch retinal vein occlusion and macroaneurysms.
BACKGROUND: Macroaneurysms can represent common consequences of branch retinal vein occlusion (BRVO). The aim of the present study is to evaluate the clinical and angiographic aspects of 31 cases of branch retinal vein occlusions (BRVO) in which retinal macroaneurysms developed, in an attempt to analyze their pathogenic features. METHODS: One hundred and sixty-one consecutive patients affected by BRVO were considered. Each patient underwent an opthalmological examination including fluorescein angiography, at an average interval of two months (range: 1-4 months) from the onset of the disease, with a mean follow-up of 43 months (range: 32-56 months). The macroaneurysms were subdivided according to size into small (from 100 to 149 microns), medium (from 150 to 249 microns), and large (greater than 250 microns), and according to origin into arterial, venous, capillary and collateral-associated. RESULTS: Thirty-one patients (19.3%) developed retinal macroaneurysms. The total number of detected macroaneurysms was 51; ten (19.6%) were large, 21 (41.2%) were of medium-size and 20 (39.2%) were small in dimension. Three lesions were of arterial origin, 22 were capillary and 26 were from collateral vessels. In 27 patients (87.1%) the lesions were located outside the macular region, and in 4 patients (12.9%) in the macular region. Patients with retinal macroaneurysms did not show a different prevalence of capillary non-perfusion when compared with others. With regard to the number of retinal venous collaterals patients with macroaneurysms developed fewer than other patients, and the difference was statistically significant (p < 0.001). CONCLUSION: The insufficient number of retinal venous collaterals can be considered the most contributory factor in the development of macroaneurysms secondary to BRVO.
Aged↗
Role of vascular endothelial growth factor and placental growth factors during retinal vascular development and hyaloid regression.
PURPOSE: Vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are members of a large group of homologous peptides identified as the VEGF family. Although VEGF-A is known to act as a potent angiogenic peptide in the retina, the vasoactive function of PlGF in this tissue is less well defined. This study has sought to elucidate the expression patterns and modulatory role of these growth factors during retinal vascular development and hyaloid regression in the neonatal mouse. METHODS: C57BL6J mice were killed at postnatal days (P)1, P3, P5, P7, P9, and P11. The eyes were enucleated and processed for in situ hybridization and immunocytochemistry and the retinas extracted for total protein or RNA. Separate groups of neonatal mice were also injected intraperitoneally daily from P2 through P9 with either VEGF-neutralizing antibody, PlGF-neutralizing antibody, isotype immunoglobulin (Ig)-G, or phosphate-buffered saline (PBS). The mice were then perfused with fluorescein isothiocyanate (FITC)-dextran, and the eyes were subsequently embedded in paraffin wax or flat mounted. RESULTS: Quantitative (real-time) reverse transcription-polymerase chain reaction (RT-PCR) demonstrated similar expression patterns of VEGF-A and PlGF mRNA during neonatal retinal development, although the fluctuation between time periods was greater overall for VEGF-A. The localization of VEGF-A and PlGF in the retina, as revealed by in situ hybridization and immunohistochemistry, was also similar. Neutralization of VEGF-A caused a significant reduction in the hyaloid and retinal vasculature, whereas PlGF antibody treatment caused a marked persistence of the hyaloid without significantly affecting retinal vascular development. CONCLUSIONS: Although having similar expression patterns in the retina, these growth factors appear to have distinct modulatory influences during normal retinal vascular development and hyaloid regression.
Animals↗
[Studies on normal developing process of the retinal vessels and effect of oxygen on the developing retinal vessels of the young rabbit (author's transl)].
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Animals↗
Risk of developing cytomegalovirus retinitis in persons infected with the human immunodeficiency virus.
This study examines the risk of developing cytomegalovirus (CMV) retinitis as a function of the duration and degree of CD4+ lymphocyte depletion. A retrospective analysis of 135 persons infected with the human immunodeficiency virus (HIV) was performed. Kaplan-Meier estimates for the percentage of patients developing CMV retinitis during the 27-month study period were calculated. Twenty-six patients were diagnosed as having CMV retinitis. In 14 of these patients, T cell phenotyping was done within the 3 months preceding diagnosis. The mean CD4+ lymphocyte count for these patients was 15.6 cells/mm3 (range, 2-33/mm3). At 27 months, the percentage of patients developing CMV retinitis with baseline CD4+ lymphocyte counts of 0-50, 51-100, and 101-250 cells/mm3 was 41.9%, 26.3%, and 14.7%, respectively (log-rank test, p = 0.003). The odds ratio for developing CMV retinitis for those with baseline CD4+ lymphocyte counts of 0-50 cells/mm3 compared with those with CD4+ lymphocyte counts of 101-250 cells/mm3 was 4.62 (p = 0.002). Twenty-four patients had CD4+ lymphocyte counts of < or = 50 cells/mm3 for an average of 13.1 months prior to diagnosis. Twenty-two patients had an acquired immune deficiency syndrome (AIDS)-defining illness diagnosed for an average of 18.0 months prior to the onset of retinitis. CMV retinitis is most likely to develop in patients with AIDS when the CD4+ lymphocyte count is < or = 50 cells/mm3.
Acquired Immunodeficiency Syndrome↗
[Effects of different oxygen inhalation modes on retinal vessels development in neonatal mice].
OBJECTIVE: This study was designed to investigate the effects of different oxygen inhalation modes on retinal vessels development in neonatal mice in order to provide experimental data for proper oxygen therapy for premature infants. METHODS: A total of 144 postnatal day (P) 7 C57BL/6J mice were randomly assigned into 6 groups according to different oxygen inhalation modes (n=24). Experimental group 1 was exposed to 30%, 40%, 50%, 60% and 75% oxygen in turn for one day respectively, followed by room air exposure for 5 days. Experimental group 2 was exposed to 75%, 60%, 50%, 40% and 30% oxygen in turn for one day respectively, followed by room air exposure for 5 days. Experimental group 3 was exposed to 75% oxygen for 5 days, followed by room air exposure for 5 days. Experimental group 4 was exposed to 75% oxygen for 5 days, 50% oxygen for 2 days and 30% oxygen for 2 days, then room air exposure for 6 days. The supplemental 75% oxygen and room air recovering was performed alternately for the mice in Experimental group 5 for 3 times and then room air exposure for 5 days. The Control group was exposed to room air for consecutive 10 days. The retinal vascular development and proliferation were evaluated by the retinal flat-mounts (ADPase stained retina) and cross-section. RESULTS: The peripheral vascular pattern was clear, and a few avascular areas were seen in the Control group at P12. At P14 the avascular area disappeared. At P17, the entire vascular pattern became completely normal. In the Experimental groups 1, 3 and 5, the central vessels became tortuous and constricted and the central avascular area increased at P12. At P14, neovascularization was seen peaking at P17 in the Experimental groups 1, 3 and 5. In the Experimental group 4, the central avascular area increased and neovascularization was seen at P14, but the central avascular area was reduced and abnormal neovascularization disappeared, with slight constriction of the deep vessels, at P17. Five days later the vascular pattern became almost normal in the Experimental group 4. The retinal vascular form of the Experimental group 2 was similar to that of the Control group. The average number of neovascular nuclei extending into the vitreous per cross-section in the Experimental groups 1, 2, 3, 4, and 5 and the Control group was 49.50 +/- 1.36, 5.17 +/- 0.67, 47.68 +/- 4.70, 5.74 +/- 2.37, 29.15 +/- 2.48, and 1.22 +/- 0.20 respectively. There were significant differences between the Experimental groups 1, 3, 5 and the Control group (P < 0.05). CONCLUSIONS: The effects of different oxygen inhalation modes on the retinal vessels development in neonatal mice were different. The obvious fluctuation of inhaled oxygen concentration and abrupt stop of supplemental oxygen after high levels of supplemental oxygen may severely affect the development of retina vascular, leading to the pathologic changes similar to retinopathy of prematurity.
Animals↗
Preferred retinal locus development in patients with macular disease.
OBJECTIVE: To observe the development of the preferred retinal locus (PRL) in a group of patients with central scotomas caused by recent onset macular disease (MD). DESIGN: Prospective observational case series. PARTICIPANTS: Twenty-five individuals with bilateral central scotomas caused by MD. All patients had experienced visual loss in their better eye in the 2 weeks before recruitment. METHODS: Patients were assessed at baseline and at 4 further visits for up to 12 months. At each visit, the retinal area used for fixation was assessed using a scanning laser ophthalmoscope, the infrared Gazetracker was used to determine the number of discrete retinal areas used for fixation in 5 positions of gaze, and reading speed was measured using MN-Read-style sentences. RESULTS: All 25 patients developed a PRL within 6 months. Sixteen patients (64%) made an adaptation whereby they were unaware of using an eccentric retinal area for fixation. Multiple fixation loci were exhibited by 11 patients at the end of the study. Nineteen patients used a consistent number of PRLs under all positions of gaze. Reading speed was not associated with PRL location or the presence of multiple PRLs. CONCLUSIONS: All of the patients in this study developed a repeatable preferred retinal locus within 6 months of visual loss in their second affected eye. Reading performance was better in patients who were not aware of using eccentric viewing strategies and who used a repeatable number of PRLs under all positions of gaze. These findings are relevant for counseling patients with MD and for the design of rehabilitation programs for patients with central vision loss.
Adaptation, Ocular↗
Possible roles of spontaneous waves and dendritic growth for retinal receptive field development.
Several models of cortical development postulate that a Hebbian process fed by spontaneous activity amplifies orientation biases occurring randomly in early wiring, to form orientation selectivity. These models are not applicable to the development of retinal orientation selectivity, since they neglect the polarization of the retina's poorly branched early dendritic trees and the wavelike organization of the retina's early noise. There is now evidence that dendritic polarization and spontaneous waves are key in the development of retinal receptive fields. When models of cortical development are modified to take these factors into account, one obtains a model of retinal development in which early dendritic polarization is the seed of orientation selectivity, while the spatial extent of spontaneous waves controls the spatial profile of receptive fields and their tendency to be isotropic.
Dendrites↗
Postnatal development of retinal projections in the brushtailed possum, Trichosurus vulpecula.
The postnatal development of retinal projections was studied in the brushtailed possum, Trichosurus vulpecula. [3H]proline was injected into one eye of 13 young possums aged 24-84 days in order to trace retinal pathways. The dorsal lateral geniculate nucleus (LGNd) can be identified in Nissl material at 19 days but not at 9-10 days. By 40 days some cytoarchitectural lamination of the LGNd is apparent and by 71 days the adult pattern of cell layers is present. At 24 days retinal fibers occupy by lateral part of the LGNd on both sides of the brain. By 38-40 days the retinal fibers fill be contralateral LGNd and the binocular part of the ipsilateral LGNd and there is a beginning of the segregation of retinal fibers into left and right eye territories. By 49-50 days a partial segregation is achieved, and complete segregation by 71 days. At 9-10 days the superior colliculus is not differentiated into layers and there is a thick zone of cell proliferation around the ventricle. By 23 days the superior colliculus has well-defined cell layers and there is still some indication of cell proliferation around the ventricle. By 40 days, the superior colliculus shows little evidence of cell proliferation. At 24 days retinal fibers fill the superficial layers of the contralateral optic tectum and are lightly distributed through the superficial layers of the rostral half of the ipsilateral tectum. By 38 days the ipsilateral retinal input is restricted to the deeper layers of the tectum. These results show that the adult pattern of retinal projections to the LGNd and optic tectum develops a number of weeks before eye opening occurs (at 90-120 days).
Aging↗
Dendritic development of retinal ganglion cells after prenatal intracranial infusion of tetrodotoxin.
The dendritic form of a cell may be established by many factors both intrinsic and environmental. Blockade of action potentials along the course of axons and in their postsynaptic targets dramatically alters the development of axonal morphology. The extent to which blockade of target cell activity retrogradely alters the dendritic morphology of the presynaptic cells is unknown. To determine whether the establishment of dendritic form by developing retinal ganglion cells depends on activity within their targets, the sodium channel blocker, tetrodotoxin (TTX), was administered via minipumps to the diencephalon of cat fetuses from embryonic day 43 (E43) to E57. At E57 retinae were removed and living retinal ganglion cells injected in vitro with Lucifer yellow to reveal their dendritic morphology. In the TTX-treated animals both alpha and beta types of retinal ganglion cells were present, as were putative gamma cells. Overall, the dendrites of retinal ganglion cells in TTX-treated animals appeared qualitatively and quantitatively similar to those of untreated animals. The only significant change in the TTX-treated cases was a small increase in the number of dendritic spines on the non-beta cells. These results indicate that the acquisition of basic dendritic form of developing ganglion cells is not influenced by the action potential activity within their targets, and that it is also independent of the terminal branching patterns of their axons.
Action Potentials↗
[Etiopathogenic consideration in the development of retinal detachment in aphakic and pseudoaphakic eye].
PURPOSE: Is to evaluate the risk factors implicated in the development of retinal detachment in aphakic and pseudophakic eyes. MATERIAL AND METHOD: We studied 46 cases operated for cataract by planned extracapsular cataract extraction with or without intraocular lens, wich developed after the operation retinal detachments. RESULTS: Retinal detachment appeared in 2.98% cases of EEC with AC-IOL and in 0.56% in EEC with PC-IOL. We performed Yag laser capsulotomy in 4 cases. Retinal detachment appeared in 12 cases between 6-12 months. The most frequent breaks causing retinal detachment where "horse shoe tears" in 23.4% of cases and tears in 14.89% cases. CONCLUSIONS: 1. High myopia and peripheral retinal degenerations are risk factors in the development of retinal detachment after the cataract operation. 2. Vitreous loss facilitates the appearing of vitreo-retinal tractions followed by retinal detachment. 3. PC-IOL reduces the frequency of retinal detachment by the stabilisation of the eye and limiting the ophthalmodonesis.
Adolescent↗
Retinal dystrophy: development retarded by galactose feeding in spontaneously hypertensive rats.
Retinal photoreceptor cell dystrophies have been widely observed in humans and in animals, but pathogenetic mechanisms are known in only a few such disorders, and successful therapeutic intervention has been reported in fewer still. Spontaneously hypertensive albino rats develop a retinal photoreceptor cell dystrophy with onset late in the first year or early in the second year of life. Between 60 and 70 percent of the animals are affected. A substantial reduction in the prevalence and severity of the dystrophy occurred in such animals whose diet contained 30 percent (by weight) D-galactose. Neither an inhibitor of the enzyme aldose reductase, present in the diet, nor diabetes mellitus, induced by streptozotocin, had any statistically significant influence on the dystrophy. Ambient light and systolic blood pressure levels also did not seem to influence the course of the disorder. The mechanism by which galactose exerts its effect is unknown, but a mutant enzyme with an elevated Michaelis constant (Km) for galactose is plausible.
Age Factors↗
Involution of retinopathy of prematurity after laser treatment: factors associated with development of retinal detachment.
PURPOSE: To identify specific features during the process of involution of retinopathy of prematurity after treatment at threshold that are associated with development of a retinal detachment. DESIGN: Retrospective case series. METHODS: The evolution of retinal detachments over time was analyzed retrospectively in 262 treated eyes of 138 infants. Specific features hypothesized to be associated with development of a retinal detachment were analyzed, including vitreous organization defined as clinically important, active stage 3 disease and active plus disease more than 21 days after treatment, and vitreous hemorrhage defined as clinically important. RESULTS: A retinal detachment developed in 36 (13.7%) of 262 eyes. Vitreous organization meeting our clinically important definition was associated with a 31-fold (confidence interval [CI] 5.37-183.63; P < .0001) and 13-fold (CI 2.97-58.59; P < .0001) increase in the odds for retinal detachment for right and left eyes, respectively. Vitreous hemorrhage defined as clinically important was associated with a 38-fold (CI 2.69-551.19; P = .007) and 15-fold (CI 1.65-144.12; P = .02) increase in the odds for retinal detachment for right and left eyes, respectively. The timing of retinal detachment relative to vitreous hemorrhage was not determined. Prolonged activity of Stage 3 disease or plus disease more than 21 days after treatment was not associated with development of a retinal detachment. CONCLUSIONS: Clinically important vitreous organization and vitreous hemorrhage were predictive for development of a retinal detachment. Evaluation of preemptive reintervention strategies for eyes at highest risk for developing a retinal detachment may be reasonable.
Female↗
Reproducibility and clinical application of a newly developed stabilized retinal laser Doppler instrument.
PURPOSE: To describe a newly developed stabilized retinal laser Doppler instrument, to report the reproducibility of retinal blood flow measurements, and to present examples of its clinical application. DESIGN: Experimental study. METHODS: The intrasession, intersession, and interobserver reproducibility of retinal blood flow measurements obtained using the Canon Laser Blood Flowmeter model CLBF 100 was assessed. Intrasession: the coefficients of variation (CV) for repeated measurements (5X) of retinal vessel diameter (D), time-average centerline blood velocity (V(av)), and blood flow (F) were calculated at 18 sites along temporal retinal arteries and 18 sites along temporal retinal veins using both eyes in six healthy volunteers. Intersession: the correlation coefficients and average differences between two sets of measurements at the same 36 retinal sites made by one examiner on two different days were calculated. Interobserver: the correlation coefficients and average differences between two sets of measurements at nine sites (five arterial and four venous) in five eyes of five of the volunteers made by two examiners on the same day were calculated. Results from two patients, one with branch retinal vein occlusion (BRVO), and one with central retinal vein occlusion (CRVO), are used to illustrate abnormal retinal circulatory characteristics. RESULTS: intrasession: CV (mean +/- SD) for D, V(av), and F were 5.5% +/- 2.2%, 13.1% +/- 6.3%, and 13.8% +/- 4.7% in arteries and 3.5% +/- 2.1%, 11.9% +/- 5.9%, and 12.7% +/- 5.5% in veins. Intersession/interobserver: strong correlations between measurements made by one examiner on two different days and by two examiners on the same day were found in D, V(av), and F. Average differences in F were 16.4% +/- 12.8% for intersession and 12.6% +/- 7.0% for interobserver comparisons. Results from the patient with BRVO show marked differences in flow characteristics in the affected quadrant compared with an unaffected quadrant in the same eye, and to the fellow eye. Results from the patient with CRVO show a dramatic improvement in flow characteristics after clearing of the occlusion. CONCLUSIONS: The reproducibility results and the fact that blood flow is measured in actual units of microl/min indicate that the instrument can be used for reliable comparison of blood flow characteristics at different retinal vascular sites in the same eye, at comparable sites in both eyes, and for comparison between patients and healthy control subjects.
Adult↗
Early retinal vessel development and iris vessel dilatation as factors in retinopathy of prematurity. Cryotherapy for Retinopathy of Prematurity (CRYO-ROP) Cooperative Group.
OBJECTIVE: To determine whether the extent of retinal vessel development present on early screening examinations for retinopathy of prematurity has prognostic value? DESIGN: The prospectively collected data from the Multicenter Trial of Cryotherapy for Retinopathy of Prematurity were used to compare the development of acute retinopathy of prematurity and long-term structural and visual outcomes for eyes with differing extents of retinal vessel development. PATIENT: Study patients had eyes with the following vessel development. In zone I eyes, vessels extended from the disc less than twice the distance from the disc to the macula. In zone II eyes, vessels extended beyond zone I but not to the nasal ora serrata. Transitional eyes had vessels partly in zone I and partly in zone II. RESULTS: The chance of developing threshold retinopathy of prematurity was inversely related to the early degree of vessel development: 54% for zone I eyes, 25% for transitional eyes, and 8% for zone II eyes. The presence of prominent iris vessels at 34 to 35 weeks of postmenstrual age was associated with increased risk for all three groups; zone I eyes almost always needed treatment (94%). The chance of having an unfavorable anatomic alteration of the posterior fundus, or poor vision at the ages of 1 year and 3 1/2 years, was also inversely related to the degree of early vessel development. Vessel development was an independently important factor even when birth weight, gestational age, and race were considered. CONCLUSIONS: The degree of early retinal vessel development is a significant predictor of outcome from retinopathy of prematurity. Iris vessel dilatation is an important indication for greater vigilance in following these infants.
Cryosurgery↗