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The authors report two patients with AIDS and cytomegalovirus retinitis who developed disc neovascularization. The disc neovascularization regressed spontaneously over several months and did not cause vitreous hemorrhage or visual loss.
There is much evidence that pigment-epithelium-derived factor (PEDF) is a potent antiangiogenic cytokine which inhibits retinal and choroidal neovascularization by inducing apoptosis in activated vascular endothelial cells. Furthermore, the regulation of PEDF appears to be linked to the regulation of vascular endothelial growth factor (VEGF), one of the most potent inducers of intraocular neovascularization. Previous studies have established that thermal photocoagulation, the mainstay in the therapy of various neovascular diseases of the posterior segment, results in a decrease in intraocular concentrations of VEGF and other angiogenic growth factors, thereby inhibiting active retinal neovascularization. In the current study, we sought to determine whether thermal photocoagulation has the potential to regulate the expression of PEDF in human retinal pigment epithelial (RPE) cells. Cultures of RPE cells were photocoagulated with a 532-nm diode laser. Subsequently, RNA was isolated for RT-PCR, and whole-cell extracts and precipitated cell culture supernatant were subjected to Western blot analysis. According to our results, PEDF mRNA and protein are significantly upregulated after photocoagulation. Moreover, PEDF protein was found to be secreted in the cell culture medium.
Insulin-like growth factor I (IGF-I) and vascular endothelial growth factor (VEGF) levels are correlated with retinal ischemia-associated intraocular neovascularization in humans. Since VEGF is required for iris and retinal neovascularization in animal models of retinal ischemia, we tested whether IGF-I could act as an indirect angiogenic factor by increasing VEGF gene expression. IGF-I increased retinal pigment epithelial (RPE) cell VEGF mRNA in a concentration-dependent manner with an EC50 of 7 nmol/1 (53.6 ng/ml). RPE and bovine smooth muscle cells exposed to 50 nmol/l (383 ng/m1) IGF-I achieved peak VEGF mRNA expression within 2 h. IGF-I-treated RPE cells increased VEGF protein levels in conditioned media and stimulated capillary endothelial cell proliferation. Blockade of the IGF-I receptor with a neutralizing antibody abrogated the VEGF increases in RPE cells. Further, hypoxia-mediated and IGF-I-mediated increases in VEGF mRNA and protein levels were additive in RPE cells, and the hypoxia-induced VEGF increases were independent of endogenous IGF-I. VEGF promoter activity was enhanced by IGF-I in RPE cells, but VEGF transcript half-life was unaltered. In summary, the supplementation of RPE and smooth muscle cell cultures with IGF-I at 5-100 nmol/l increased VEGF mRNA and secreted protein levels. The VEGF increases in RPE cells occurred primarily through enhanced transcription of the VEGF gene and via the IGF-I receptor. Elevated IGF-I levels may promote neovascularization through increased retinal VEGF gene expression.
To clarify the healing process of subretinal neovascularization (SRN) histopathologically following laser photocoagulation treatment, we performed laser photocoagulation for experimental SRNs produced in rhesus monkey eyes. To produce long-lasting SRNs, 0.5M 1-ornithine hydrochloride solution was injected intravitreously 2 weeks after photocoagulation. These SRNs were treated a 590nm dye laser, and examined clinically and histopathologically at 24 hours, 2 weeks, 3 months. Histopathologically, new vessels in the subretinal space were coagulated intensely and disappeared during the course of healed lesion. In these lesions, the retinal pigment epithelial cells proliferated in the subretinal space after the disappearance of the SRNs and covered the scar tissue. In strongly coagulated lesions, glial cells were related to the formation of scar tissue. These results showed that closure of new vessels was necessary for the healing of SRNs by photocoagulation and proliferation of the retinal pigment epithelial cells and glial cells occurred during their healing process.
An immunohistological study was performed on 6 specimens of subretinal membranes obtained surgically from patients suffering from age-related disciform macular degeneration. using immunoperoxidase procedures, we found in those membranes large amounts of IgG, IgA and IgE as well as C1q, C3c and C3d complement components diffusely distributed in the connective stroma and within the new blood vessel walls. Moreover, subretinal membranes contained numerous isolated HLA-DR- and -DQ-expressing cells, including glial, pigment epithelial and vascular endothelial cells. Monoclonal antibodies to immunocompetent cells disclosed only rare B and natural killer lymphocytes or suppressor-cytotoxic T cells, as well as some monocytes. These results show that immune phenomena are involved in proliferative changes associated with subretinal neovascularization. In addition, they suggest there are interactions between the immune system and peptide growth factors.
A modified classification of cicatricial RLF has been presented. Particular emphasis is placed on myopia, one of the hallmarks of grade i cicatricial RLF. Whether or not this is axial myopia is still open to question, but since the more myopic eye was usually longer by ultrasonic measurement than the less myopic eye, actual enlargement of the eye must play some role. Other features noted in grade I RLF were retinal pigmentation, vitreous membranes, and equatorial retinal folds. In grade II the most significant finding was dragging of the retina. It was noted that in all cases of dragging of the retina there were also peripheral retinal changes. Even more important, however, was the fact that peripheral retinal changes are often present when there are no changes in the posterior pole. Neovascularization, elevated retinal vessels, lattice degeneration, and retinal breaks were other features of grade II retinopathy. Significant was the fact that the incidence of lattice in patients with cicatricial RLF (15%) was more than twice that of the normal population. Grade III RLF was characterized by falciform retinal folds, and grade IV, by retinal detachment. Thirty-nine retinal detachments were rhegmatogenous and usually had temporal retinal breaks. Retinal detachments of a tractional exudative variety (14 eyes) tended to occur earlier in life than the rhegmatogenous variety. In infants, they were preceded by increased tortuosity of the vessels in the posterior pole and, sometimes, accumulation of exudation, both ominous prognostic signs.
180 consecutive patients with exudative age-related macular degeneration and clinical signs of subretinal neovascular membranes were examined by scanning laser fluorescein angiography. This technique demonstrated well-defined, newly formed subretinal vessels in approximately 50%, ill-defined subretinal vessels in approximately 20%, and not visible or occult subretinal vessels in the remaining 30% of the patients. Patients with ill-defined or occult neovascular membranes were also examined with scanning laser infrared angiography with cardiogreen. Newly formed subretinal vessels were well defined in approximately 40% of these patients, and ill defined in 23%. In 37% of the patients, neovascularizations were also not visible with infrared angiography. Results of scanning laser infrared angiography seem to be superior to earlier methods of infrared angiography. Conditions are discussed under which fluorescein and cardiogreen angiography can demonstrate subretinal membranes in age-related maculopathy.
We report the clinical history of 2 patients affected with reticular dystrophy of the retinal pigment epithelium and central choroidal neovascularization. With time, spontaneous reduction of the subretinal fluid associated with consequent improvement of the visual acuity has been noted in our first case. The second patient showed a stable fibrotic subfoveal choroidal neovascularization. Conventional fluorescein angiography and indocyanine green videoangiography findings are illustrated. The differential diagnosis between other reticular pigmented lesions often associated with choroidal neovascularization is discussed.
PURPOSE: It has been reported that 17beta-estradiol (E2) may enhance the proliferation of bovine retinal vascular endothelial cells (BRECs) by increasing the expression of VEGFR-2 and VEGF. The hypothesis in the current study was that estrogen may contribute to fetal vascular development and the cessation of exposure to estrogen of premature infants on birth may have an inhibitory effect on retinopathy of prematurity (ROP). Because ROP is thought to develop under relative hypoxia after exposure to high-dose oxygen, this study was conducted to investigate how estrogen modulates hypoxia-induced VEGF in BRECs and mouse ROP. METHODS: Gene expression of VEGF and hypoxia-inducible factor (HIF)-1alpha were studied in BRECs, with or without E2, under normoxia and hypoxia (1% O2). A binding assay was performed to determine whether estrogen interferes with HIF-1-mediated induction of VEGF. In a mouse ROP model, effects of E2 were evaluated by avascular area, subsequent extraretinal neovascularization, and retinal expression of the VEGF gene, by administering E2 during hyperoxia (75% O2) and/or after exposure to room air. RESULTS: Hypoxia-induced VEGF mRNA in BRECs was reduced dose dependently by 1 to 100 nM E2. E2 reduced hypoxia-induced binding of HIF-1 to the VEGF promoter site and reduced the HIF-1alpha mRNA level. In mouse ROP, injection of E2 during hyperoxia increased retinal VEGF mRNA and reduced the retinal avascular area at the end of hyperoxia. E2 treatment during the normoxia that followed reduced VEGF mRNA and extraretinal neovascularization. Treatment with E2 throughout both periods significantly improved retinopathy. CONCLUSIONS: Estrogen may function as a significant modulator of the level of VEGF mRNA under different oxygen conditions and could serve as a prophylactic agent for ROP.
PURPOSE: To report a case of Bartonella henselae infection. DESIGN: Observational case report. METHODS: Review of the clinical, laboratory, photographic, and angiographic records of a patient with cat scratch disease associated with central retinal artery and vein occlusion, neovascular glaucoma, and severe vision loss. RESULTS: A 21-year-old man had no light perception in the left eye secondary to concurrent central retinal artery and vein occlusion believed to have resulted from infection with Bartonella henselae. Forty days later, he developed neovascular glaucoma in the left eye. CONCLUSION: Ocular complications associated with Bartonella henselae infection may include central retinal artery and vein occlusion, neovascular glaucoma, and severe vision loss.
PURPOSE: To report the outcome of a patient with a subretinal neovascular membrane secondary to idiopathic juxtafoveolar retinal telangiectasis treated with photodynamic female therapy. METHODS: Interventional case report. A 43-year-old female with type 2A idiopathic juxtafoveolar retinal telangiectasis presented with a 2-week history of decreased vision and a subretinal neovascular membrane in the left eye. RESULTS: Visual improvement from 20/70-2 to 20/50-2 in the left eye was observed after two photodynamic therapy treatments of a juxtafoveal subretinal neovascular membrane with verteporfin, and was maintained through 7 months of follow-up. Fluorescein angiography showed no leakage specific to the subretinal neovascular membrane, but leakage from the juxtafoveal telangiectasis continued. CONCLUSION: A substantial improvement was seen in this patient after treatment of the juxtafoveal subretinal neovascular membrane by photodynamic therapy. Given the poor prognosis of these lesions, photodynamic therapy may therefore be a useful treatment for patients with subretinal neovascular membranes associated with idiopathic juxtafoveolar retinal telangiectasis.
PURPOSE: To analyze the results of photodynamic therapy (PDT) in bilateral acquired parafoveal telangiectasis. DESIGN: Interventional cases report. METHOD: Retrospective analysis of visual acuity measured with ETDRS charts and of fluorescein angiography findings for two women in whom the eye with lesser visual acuity was treated by PDT for bilateral acquired parafoveal telangiectasis without subretinal neovascularization. RESULTS: Initial visual acuity of the treated eye was 20/63 in both patients and did not change significantly for 3 to 6 months after one session of PDT. Fluorescein angiography in both cases and optical coherence tomography in one case also appeared unchanged. No adverse effect has been observed. CONCLUSIONS: Photodynamic therapy was not beneficial for the outcome of these patients with bilateral acquired telangiectasis, because it improved neither their visual acuity nor their macular edema.
The electron microscopy of 14 samples of epiretinal membranes obtained in the course of transciliary vitrectomy performed in proliferative diabetic retinopathy (PDR) showed a majority of neovascularized vessels to be represented by those of the venular type or capillaries. It can be concluded on the basis of examination results that the structures of neovascularized vessels can be highly diverse in diabetic retinopathy, which depends on a variety of factors: 1) proliferation stage; 2) division of the microcirculation bed; and 3) end of the epiretinal membrane where a given vessel is located as to the growth epicenter. Finally, described are both neo-vessels with a virtually normal structure of the vascular wall and atrophying vessels. The signs of vascular reduction grow to be more pronounced at later stages.
OBJECTIVE: To report the visual outcome in patients with a neovascular membrane (NVM) associated with idiopathic juxtafoveolar telangiectasis (IJFT). METHODS: We performed a retrospective, noncomparative analysis of 26 eyes of 16 patients with an NVM associated with bilateral IJFT (Gass classification group 2A). Eyes were divided into 2 groups: group WO (n = 11) included eyes with IJFT without evidence of an NVM on initial examination; eyes in group W (n = 15) had an NVM at the initial diagnosis of IJFT. In group WO, the initial visual acuity and the time between the initial examination to the diagnosis of an NVM were evaluated. Characteristic fundus findings, including the presence or absence of a chorioretinal anastomosis, intraretinal pigmentary plaques, and crystalline deposits, as well as the final visual acuity were reviewed for both groups. RESULTS: The initial visual acuity for eyes in group WO ranged from 20/20 to 20/70 (median, 20/30); in group W, from 20/20 to 4/200 (median, 20/70). The average time from initial diagnosis of IJFT to the development of an NVM was 73 months (range, 5-142 months). In group WO, chorioretinal anastomosis and concurrent perivascular retinal pigment epithelial hyperplasia were observed before the development of an NVM. The final visual acuity for all eyes ranged from 20/40 to 2/200 (median, 20/200). Eighty-one percent of eyes (21/26) had a final visual acuity of 20/200 or worse. CONCLUSIONS: The stable final visual acuity in patients with an NVM associated with IJFT is generally poor, with 80% of eyes in this series having a final visual acuity of l20/200 or worse. In patients with IJFT, the presence of a chorioretinal anastomosis and retinal pigment epithelial hyperplastic plaques always preceded the development of an NVM.
Subretinal neovascular membranes (SRNVM) in the pediatric population are rare. The clinical presentation, etiology, course, and management of SRNVM in 25 children (27 eyes) were studied retrospectively. Inflammatory or infectious conditions predominated (10 of 25). Eleven of 19 untreated SRNVM (58%) spontaneously involuted, with 9 of these 11 achieving a final visual acuity of 20/50 or better. A hyperpigmented ring on fluorescein angiography was associated with 9 of the 11 involuted SRNVM. The presence of this pigmented ring may help to identify those cases with a better visual prognosis.
PURPOSE: Acidosis-induced retinopathy (AIR) in the neonatal rat provides an alternative model for retinopathy of prematurity (ROP). We studied the relationship of vascular endothelial growth factor (VEGF) retinal mRNA and insulin-like growth factor-1 (IGF-1) retinal mRNA expression with the emergence of neovascularization (NV) in AIR. METHODS: Two hundred seventy-five newborn Sprague-Dawley rats were raised in 11 expanded litters of 25. Using our established AIR model, acidosis was induced by twice-daily gavage with NH4Cl from day 2 to day 8 of life (n=175). Rats were sacrificed at days 5, 8, and 10. Nongavaged rats were used as age-matched controls (n=100). Retinae from left eyes were dissected, flatmounts were ADPase-stained, and the presence and severity of NV was scored in a masked manner. Individual right retinae were processed for analysis of retinal VEGF and IGF-1 mRNA using quantitative real-time reverse-transcriptase PCR (qRT-PCR). RESULTS: Retinal VEGF mRNA was increased 1.4-fold at day 10 in AIR, when compared with age-matched controls (p=0.03). This correlated with maximal NV at day 10 in AIR. Retinal IGF-1 mRNA was decreased to 82% of its normal expression on day 8 (p=0.006), prior to maximal NV, before returning to normal expression at day 10, when compared with nonacidotic controls. CONCLUSIONS: In AIR, preretinal neovascularization is associated with decreased retinal IGF-1 mRNA prior to maximal NV and increased retinal VEGF mRNA at the time of maximal NV. These growth factor changes in AIR are similar to those seen with hypercarbic oxygen-induced retinopathy. The retinal IGF-1 pathway may provide an alternative target for therapeutic intervention in abnormal retinal angiogenesis.
Degenerative changes in the retinal pigment epithelium (RPE) may compromise the patient's visual acuity before the development of frank choroidal (subretinal) neovascularization. A decompensation of the barrier function of the RPE may permit accumulation of subretinal fluid and sub- or intraretinal hard, yellow exudate. Laser treatment may control this inimical process which threatens or impairs vision and may prevent or delay its progression.
PURPOSE: To evaluate the efficacy and safety of transpupillary thermotherapy (TTT) for subfoveal neovascularization (SRNVM) in patients with group 2A Idiopathic Juxtafoveolar Telangiectasis (IJFT). DESIGN: Nonrandomized interventional case series. METHODS: We performed TTT for subfoveal SRNVM in 14 eyes of 13 patients with group 2A IJFT, who were referred to our tertiary care center. We evaluated visual outcome and SRNVM closure rate in these patients. RESULTS: After a mean follow-up period of 8.65 months, 92.3% of treated eyes had stabilization or improvement in visual acuity as well as regression of SRNVM by fluorescein angiography (FA). One SRNVM showed persistent leakage. One patient worsened by more than 2 Snellen lines; one required retreatment. CONCLUSION: Transpupillary thermotherapy may be a safe and useful alternative treatment option for patients with group 2A IJFT with subfoveal SRNVM.