Subretinal Neovascularization Research Articles

Photodynamic therapy for subretinal choroidal neovascularization in patients with multifocal choroiditis

Objective To observe the clinical effect of photodynamic therapy (PDT)based comprehensive treatment for choroidal neovascularization (CNV) in patients with multifocal choroiditis (MC).Methods Nine eyes of 8 MC patients (7 females and 1 male) with CNV who had undergone PDT based comprehensive treatment were enrolled in this study.The patients aged from 25 to 54 years with the mean of (41.8±10.6) years.The examinations of best-corrected visual acuity (BCVA),slit lamp microscope,indirect ophthalmoscopy,fundus fluorescein angiography and optical coherence tomography were performed.The BCVA ranged from 20/333 to 20/50 (mean logMAR 0.68±0.32).The mean CNV area was (0.767±0.445) mm2.The central retinal thickness (CRT) was (355.2±65.2) μm.Among the 8 patients,4 eyes received only PDT,2 eyes received PDT and oral corticosteroid,1 eye received PDT and intravitreal injection of 1.25 mg bevacizumab,2 eyes received PDT and subtenon injection of 40 mg triamcinolone acetonide.The follow-up period ranged from 3 to 22 months,with the mean of (14.0± 5.7)months.The BCVA,mean CNV area and CRT before and after treatment were analyzed.Results By the end of last visit,the BCVA improved to 20/250 to 20/25 (mean logMAR 0.58±0.37),but the difference was not statistically significant (t=1.890,P=0.095).Visual acuity improved 3 lines in 3 eyes (33.3 ％),improved 1.5 lines in 1 eye ( 11.1 ％),unchanged in 4 eyes (44.4 ％ ) and decreased 1.5 lines in 1 eye (11.1 ％ ).The mean CNV area decreased to (0.684 ± 0.371) mm2,but the difference was not statistically significant (t=0.996,P=0.349).The CRT decreased to (295.3±79.4) μm,but the difference was not statistically significant (t=2.242,P=0.055).Conclusion PDT can stabilize visual acuity in patients with subretinal CNV secondary to MC,especially when combined with intravitreal injection of anti-vascular endothelial growth factor drugs or steroid. Key words: Choroidal neovascularization/therapy; Photochemotherapy; Choroiditis/complications

INTRAVITREAL BEVACIZUMAB FOR TREATMENT OF PROLIFERATIVE AND NONPROLIFERATIVE TYPE 2 IDIOPATHIC MACULAR TELANGIECTASIA

To determine the effect of treatment with intravitreal bevacizumab on retinal thickness and visual acuity in the nonproliferative and proliferative forms of Type 2 idiopathic macular telangiectasia. Retrospective chart review of clinic patients treated with bevacizumab for macular telangiectasia Type 2. Treatment was performed until no further changes were seen after repeated bevacizumab injections. All patients had Snellen visual acuity testing, fundus fluorescein angiography, and measurement of central macular thickness by optical coherence tomography at baseline. Visual acuity and central macular thickness were recorded at follow-up visits. Fourteen eyes of 10 patients were included. In 5 eyes with nonproliferative macular telangiectasia Type 2, average follow-up was 17 months (± 7 months), and no eye demonstrated improvement in visual acuity or decrease in central macular thickness at final follow-up compared with baseline. In 9 eyes with proliferative disease, follow-up averaged 17 months (± 9 months). At 6 weeks, central macular thickness decreased 63 μm (± 58 μm), and acuity improved 1.7 lines (± 2 lines). At final follow-up, central macular thickness decreased 48 μm (± 89 μm) and acuity improved 1.1 lines (± 3 lines). Subretinal neovascularization resolved in eight of nine eyes with proliferative disease after treatment. Bevacizumab did not improve acuity or reduce retinal thickness in nonproliferative macular telangiectasia Type 2 at final follow-up. In proliferative macular telangiectasia Type 2, bevacizumab caused involution of neovascularization and improved visual acuity.

Intravitreal ranibizumab in the treatment of subretinal neovascularization in a case of punctate inner choroidopathy

AbstractPurpose To report a case of a subretinal neovascular membrane in a bilateral retinal lesions compatible with punctate inner choroidopathy (PIC) treated with intravitreal ranibizumab obtaining excellent results.Methods A 28‐year old woman suffering loss of visual acuity with her left eye, who presented an image suggestive of subretinal neovascular membrane in her left eye and bilateral retinal lesions compatible with punctate inner choroidopathy(PIC).Results In this situation it was decided to initiate treatment with intravitreal ranibizumab in OD,(monthly for a total of three injections). The visual acuity improved to 20/30 after 1 st injection. One month after the third injection, the BCVA was 20/20 and remained stable. During the year the patient has been followed in our department were no new symptoms or signs of activity.Conclusion The differential diagnosis must be made between PIC and the rest of “white dot syndromes" and the presumed ocular histoplasmosis syndrome (POHS). Angiogenic drugs may be a good alternative for the treatment of such diseases when they develop a subretinal neovascular membrane.

A potential therapeutic strategy for inhibition of ocular neovascularization with a new endogenous protein: rhEDI-8t

Endogenous angiogenesis inhibitors act as natural negative feedback in the focal area during the neovascularization process, and have less interference on physiological angiogenesis, and thus fewer negative side-effects. These inhibitors are potential candidates to combine with or substitutes for current popular anti-angiogenesis treatments to have synergistic effect. In this study, the effects of recombinant endothelial growth inhibitor protein (rhEDI-8t), a novel endogenous protein originated from collagen VIII, was investigated on ocular neovascularization (NV). Endostatin, a well-identified endogenous angiogenesis inhibitor, was compared in parallel and served as a positive control. The inhibitory effect of rhEDI-8t on vascular endothelial cells was evaluated by a human umbilical vascular endothelial cells (HUVEC) proliferation test and a bovine aortic endothelial cells (BAEC) migration experiment. The effect of rhEDI-8t on ocular NV was further investigated in mice with choroidal neovascularization (choroidal NV) induced by laser, ischemic retinopathy and transgenic mice with expression of VEGF in photoreceptors (rho/VEGF) respectively. RhEDI-8t inhibited the growth of HUVECs and migration of BAECs stimulated by basic fibroblast growth factor (bFGF). Mice intravitreally treated with rhEDI-8t showed a significant reduction of choroidal NV, retinal NV and subretinal NV. Endogenous angiogenesis inhibitor rhEDI-8t showed a potent anti-angiogenesis effect in both in vitro and in vivo experiments. It contributed to the suppression of ocular NV. The study suggested that rhEDI-8t could be a subsidiary potent therapeutic medicine in addition to anti-VEGF therapy in future clinical anti-angiogenesis treatment.

Fundus autofluorescence patterns in type 2A idiopathic juxtafoveolar retinal telangiectasis

To describe fundus autofluorescence (FAF) patterns in patients with type 2A idiopathic juxtafoveolar retinal telangiectasia (IJRT). We reviewed FAF images, color photographs, and fluorescein angiography (FA) images of 30 eyes from 16 patients with type 2A IJRT. Eyes with presence of subretinal neovascularization or any other retinal pathology were excluded. All the imaging modalities were obtained with a Heidelberg Retina Angiograph (HRA) confocal laser scanning system. The mean age of the patients was 50.7 years, 68.5% female. At baseline, the median best-corrected visual acuity was 20/50. Loss of normal foveal hypoautofluorescence was noted in 93.3% of eyes. All the eyes showed hypoautofluorescence corresponding to intraretinal crystals and pigment clumps. Increased FAF around the pigments was noted in 93.3% of eyes. Increased FAF corresponding to the angiographic leakage from telangiectatic and nontelangiectatic areas was noted in 86.6% of eyes and 80% of eyes, respectively. Loss of foveal hypoautofluorescence and increased FAF corresponding to the nontelangiectatic angiographic leakage areas were predominant features. Fundus autofluorescence patterns corresponding to color photography and FA findings may further add to the understanding of morphologic alterations in type 2A nonproliferative IJRT at early stages.

Interleukin-1β Inhibition Prevents Choroidal Neovascularization and Does Not Exacerbate Photoreceptor Degeneration

The pro-inflammatory cytokine IL-1β has been shown to promote angiogenesis. It can have a neurotoxic or neuroprotective effect. Here, we have studied the expression of IL-1β in vivo and the effect of the IL-1 receptor antagonist on choroidal neovascularization (CNV) and retinal degeneration (RD). IL-1β expression significantly increased after laser injury (real time PCR) in C57BL/6 mice, in the C57BL/6 Cx3cr1(-/-) model of age-related macular degeneration (enzyme-linked immunoabsorbent assay), and in albino Wistar rats and albino BALB Cx3cr1(+/+) and Cx3cr1(-/-) mice (enzyme-linked immunoabsorbent assay) after light injury. IL-1β was localized to Ly6G-positive, Iba1-negative infiltrating neutrophils in laser-induced CNV as determined by IHC. IL-1 receptor antagonist treatment significantly inhibited CNV but did not affect Iba1-positive macrophage recruitment to the injury site. IL-1β significantly increased endothelial cell outgrowth in aortic ring assay independently of vascular endothelial growth factor, suggesting a direct effect of IL-1β on choroidal endothelial cell proliferation. Inhibition of IL-1β in light- and laser-induced RD models did not alter photoreceptor degeneration in Wistar rats, C57BL/6 mice, or RD-prone Cx3cr1(-/-) mice. Our results suggest that IL-1β inhibition might represent a valuable and safe alternative to inhibition of vascular endothelial growth factor in the control of CNV in the context of concomitant photoreceptor degeneration as observed in age-related macular degeneration.

Age-Dependent Retinal Iron Accumulation and Degeneration in Hepcidin Knockout Mice

Iron dysregulation can cause retinal disease, yet retinal iron regulatory mechanisms are incompletely understood. The peptide hormone hepcidin (Hepc) limits iron uptake from the intestine by triggering degradation of the iron transporter ferroportin (Fpn). Given that Hepc is expressed in the retina and Fpn is expressed in cells constituting the blood-retinal barrier, the authors tested whether the retina may produce Hepc to limit retinal iron import. Retinas of Hepc(-/-) mice were analyzed by histology, autofluorescence spectral analysis, atomic absorption spectrophotometry, Perls' iron stain, and immunofluorescence to assess iron-handling proteins. Retinal Hepc mRNA was evaluated through qPCR after intravitreal iron injection. Mechanisms of retinal Hepc upregulation were tested by Western blot analysis. A retinal capillary endothelial cell culture system was used to assess the effect of exogenous Hepc on Fpn. Hepc(-/-) mice experienced age-dependent increases in retinal iron followed by retinal degeneration with autofluorescent RPE, photoreceptor death, and subretinal neovascularization. Hepc(-/-) mice had increased Fpn immunoreactivity in vascular endothelial cells. Conversely, in cultured retinal capillary endothelial cells, exogenous Hepc decreased both Fpn levels and iron transport. The retina can sense increased iron levels, upregulating Hepc after phosphorylation of extracellular signal regulated kinases. These findings indicate that Hepc is essential for retinal iron regulation. In the absence of Hepc, retinal degeneration occurs. Increases in Hepc mRNA levels after intravitreal iron injection combined with Hepc-mediated decreases in iron export from cultured retinal capillary endothelial cells suggest that the retina may use Hepc for its tissue-specific iron regulation.

Peculiar manifestation of macular telangiectasia type 2.

The purpose of this study was to report two unusual cases of macular telangiectasia type 2 with pronounced asymmetric clinical presentations. Two patients. Observational case study. Two patients presented with acute complaints of decreased vision and metamorphopsia in one eye. Each was found to have unilateral, juxtafoveal, subretinal neovascularization and minimal or no clinical evidence of macular telangiectasia type 2 in the fellow eye. In one patient, clinical and angiographic findings of macular telangiectasia type 2 were observed in the previously unaffected eye 13 years after the initial presentation. Macular telangiectasia type 2 is a bilateral condition, but in rare cases, significant asymmetry between the two eyes concerning disease severity can occur, potentially delaying diagnosis and management.

Metabolic physiology in age related macular degeneration

Ischemia and hypoxia have been implicated in the pathophysiology of age related macular degeneration (AMD). This has mostly been based on studies on choroidal perfusion, which is not the only contributor to retinal hypoxia found in AMD eyes. Other features of AMD may also interfere with retinal oxygen metabolism including confluent drusen, serous or hemorrhagic retinal detachment, retinal edema and vitreoretinal adhesion. Each of these features contributes to retinal hypoxia: the drusen and retinal elevation by increasing the distance between the choriocapillaris and retina; vitreoretinal adhesion by reducing diffusion and convection of oxygen towards and vascular endothelial growth factor (VEGF) away from hypoxic retinal areas. Hypoxia-inducible-factor is known to exist in subretinal neovascularization and hypoxia is the main stimulus for the production of VEGF. Each feature may not by itself create enough hypoxia and VEGF accumulation to stimulate wet AMD, but they may combine to do so. Choroidal ischemia in AMD has been demonstrated by many researchers, using different technologies. Choroidal ischemia obviously decreases oxygen delivery to the outer retina. Confluent drusen, thickening of Bruch's membrane and any detachment of retina or retinal pigment epithelium, increases the distance between the choriocapillaris and the retina and thereby reduces the oxygen flux from the choroid to the outer retina according to Fick's law of diffusion. Retinal elevation and choroidal ischemia may combine forces to reduce choroidal oxygen delivery to the outer retina, produce retinal hypoxia. Hypoxia leads to production of VEGF leading to neovascularization and tissue edema. A vicious cycle may develop, where VEGF production increases effusion, retinal detachment and edema, further increasing hypoxia and VEGF production. Adhesion of the viscous posterior vitreous cortex to the retina maintains a barrier to diffusion andconvection currents in the vitreous cavity according to the laws of Fick's, Stokes-Einstein and Hagen-Poiseuille. If the vitreous is detached from the surface of the retina, the low viscosity fluid transports oxygen and nutrients towards an ischemic area of the retina, and cytokines away from the retina, at a faster rate than through attached vitreous gel. Vitreoretinal adhesion can exacerbate retinal hypoxia and accumulation of cytokines, such as VEGF. Vitreoretinal traction can also cause hypoxia by retinal elevation. Conceivably, the basic features of AMD, drusen, choroidal ischemia, and vitreoretinal adhesion are independently determined by genetics and environment and may combine in variable proportions. If the resulting hypoxia and consequent VEGF accumulation crosses a threshold, this will trigger effusion and neovascularization.

Bilateral choroidal osteoma with optic atrophy

Choroidal osteoma is a rare, yellowish-white lesion of the choroid that predominantly affects young women in the second decade of life. Subretinal neovascularization or collection of subretinal fluid may occur in 50 % or more patients in the long run. A 15-year-old girl presented to our practice with bilateral choroidal osteoma associated with advanced bilateral optic atrophy. The underlying cause for optic atrophy is unclear; possible explanations include mechanical pressure effect and ischemic damage.

Evolution of visual acuity in patients with wet type of AMD and good initial visual aquity

Abstract Purpose The evaluation of wet type of AMD after intravitreal injections with anti‐angiogenic factors in patients with good initial visual aquity. Correlation between final and initial visual acuity, as well as with the number of injections Methods 101 patients of average age 76 participated in the study. All of them suffered from wet type of AMD. Study group included 24 of them with good initial visual acuity, defined as visual acuity of 6/10 of the decimal scale or higher. The remaining 77 patients served as control group. The initial evaluation included full ophthalmologic examination, OCT imaging and fluorescein angiography. The decision for the treatment was based on the findings of the first examination and of the monthly reevaluation thereafter. Results In the 24 patients of the study group, visual acuity increased significantly from 0,61 (+/‐0,2) to 0,82 (+/‐0,2) in decimal scale or from 0,27 (+/‐0,22) to 0,14 (+/‐0,2) in LOGMAR scale (p<0,001). The average number of intravitreal injections was 4,9 in a mean monitoring time of 9 months. In this team the final visual acuity depends on the initial one (p= 0,013), but not on the number of intravitreal injections (p> 0,05). Conclusion the final visual acuity in the group with good initial visual acuity correlates well with the initial visual acuity and does not correlate with the number of injections. This finding shows the significance of early diagnosis of subretinal neovascularisation in AMD, when the vision is still high.

Redefining tissue engineering for nanomedicine in ophthalmology

Working at the nanoscale means to completely rethink how to approach engineering in the body in general and in the eye in particular. In nanomedicine, tissue engineering is the ability to influence an environment either by adding, subtracting or manipulating that environment to allow it to be more conducive for its purpose. The goal is to function at the optimum state, or to return to that optimum state. Additive tissue engineering replaces cells or tissue, or tries to get something to grow that is no longer there. Arrestive tissue engineering tries to stop aberrant growth which, if left uncontrolled, would result in a decrease in function. Nano delivery of therapeutics can perform both additive and arrestive functions influencing the environment either way, depending on the targeting. By manipulating the environment at the nanoscale, the rate and distribution of healing can be controlled. It infers that potential applications of nanomedicine in ophthalmology include procedures, such as corneal endothelial cell transplantation, single retinal ganglion cell repair, check of retinal ganglion cell viability, building of nanofibre scaffolds, such as self-assembling peptides, to create a scaffold-like tissue-bridging structure to provide a framework for axonal regeneration in the case of optic nerve reconnection or eye transplantation, and ocular drug delivery. Examples of potential arrestive therapies include gene-related treatment modalities to inhibit intraocular neovascularization and to block retinal cell apoptosis. Looking towards the future, this review focuses on how nanoscale tissue engineering can be and is being used to influence that local environment.

A Subretinal Matrigel Rat Choroidal Neovascularization (CNV) Model and Inhibition of CNV and Associated Inflammation and Fibrosis by VEGF Trap

The exudative, or the wet form of age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). A subretinal Matrigel (BD Biosciences, Bedford MA) model of CNV is described here, along with the effects of vascular endothelial growth factor (VEGF) neutralization on the development of CNV and associated inflammation and fibrosis. CNV was induced in adult Sprague-Dawley rats by subretinal injection of Matrigel. CNV growth and associated leukocyte infiltration and collagen deposition were examined. VEGF Trap (Regeneron Pharmaceuticals, Tarrytown, NY), a recombinant protein that comprises portions of the extracellular domains of VEGF receptors 1 and 2 and that binds all isoforms of VEGF-A as well as placental growth factor with high affinity, was administered subcutaneously. Initiation of CNV was detected 4 days after Matrigel injection and then increased progressively in size. Systemic administration of VEGF Trap beginning on day 2 and 6 completely prevented development of CNV. When CNV was allowed to develop for 10 days before treatment was initiated, VEGF Trap not only prevented its further progression, but also induced substantial regression of existing lesions. In addition, VEGF Trap treatment reduced the total lesion volume and largely prevented the progressive leukocyte infiltration and fibrosis associated with CNV. The subretinal Matrigel CNV model provides a convenient tool for the study of the diverse components of complex CNV lesions. The data not only confirm the critical roles of VEGF in the development and maintenance of CNV, but further demonstrate that VEGF and other VEGF receptor 1 ligands promote CNV-associated inflammation and fibrosis.

Optic Disc Abnormalities – Diagnosis, Evolution and Influence on Visual Acuity

Congenital abnormalities of the optic disc are not so rare. The etiology for the most of them is unknown. Visual acuity of affected eye may be minimally or severely affected, depending on the extent of lesion. All of these conditions can be unilateral or bilateral. Children who have unilateral optic disc abnormalities generally present during the preschool years with sensory esotropia. Visual acuity may be unaffected like in optic disc pit, optic disc drusen, fibre medullares, ect. However, during the evolution they may cause a decrease in visual acuity like serous retinal detachment in optic disc pit, atrophy or subretinal neovascularisation in optic disc drusen. Some of them like fibre medullares needs only a good diagnose and they do not have any evolution. Fluorescein angiography and ultrasonography may be crucial diagnostic procedures to discover some of them, like optic disc drusen. Optic disc abnormalities may be associated with other congenital disorders of the eye and often central nervous system malformations. Secondary they may be associated retinal detachment, retinochisis, macular edema, choroid neovascularisation and lipid exudation. Some of these conditions may be found on routine ophthalmologic exam such as optic disc drusen and fibre medullares and often are diagnostically problem. The aim of our study was to present some of our cases with different optic disc abnormalities such as fibre medullares, optic disc coloboma, hypoplasio disc, optic disc drusen and optic disc pit.

Anetoderma. A possible new risk factor for subretinal neovascularization

Editor, Anetoderma is a rare disease of the elastic connective tissue which is characterized clinically by multiple 5–25 mm-diameter round atrophic papules that bulge outwards from the skin of the trunk, the upper part of extremities and neck. At palpation, the lesions are flaccid and herniate inwards. Histopathologically, there is fragmentation of elastic fibres and loss of elastic tissue in the dermis. The aetiology of anetoderma is unknown, but the disease has been related to antiphospholipid syndrome, systemic lupus erythematosus (Venencie et al. 1984) and infections such as borreliosis (Bauer et al. 2003). In rare cases, the disease has been shown to be inherited or idiopathic. In the eye, anetoderma has been shown to be related to keratoconus, blue sclerae, pseudotumor orbitae and cataract (Brenner et al. 1977, Nuñez et al. 1995), whereas no studies have reported a relation between anetoderma and diseases in the posterior segment of the eye. A 27-year-old otherwise healthy woman with previous normal vision was referred with a 2 weeks history of metamorphopsia and blurred vision on the left eye. There was no history of trauma, choroiditis, or other known risk factors for the development of subretinal neovascularization, but anetoderma (Schweninger–Buzzy type) confirmed by skin biopsy had been diagnosed at the age of 12 years. Laboratory examinations for antinuclear antibodies (ANA), cardiolipin antibody and serological tests for Borrelia, syphilis and HIV were negative. The patient was subjected to a routine clinical examination including measurement of visual acuity, slit lamp examination, optical coherence tomography scanning and fluorescein angiography. The clinical examination showed VAD = 1.2 and VAS = 0.1 and both eyes had emmetropia. All other examinations on the right eye were normal. On the left eye, ophthalmoscopy showed central retinal oedema with haemorrhages and exudates. Optical coherence tomography (OCT) scanning of the left eye showed intra-retinal oedema with a central retinal thickness of 452 microns. Fluorescein angiography revealed a classical subfoveal neovascularization (Fig. 1). After three Intra-vitreal injections of ranibizumab on the left eye with 1 month intervals, the central retinal thickness was reduced to 214 microns and visual acuity had increased to 0.8. An early phase angiography of the normal right eye and the left eye with a subfoveal neovascularization. Subretinal neovascularization is a well documented complication to connective tissue diseases such as pseudoxanthoma elasticum and Ehlers Danlos’ syndrome and may be related to discontinuities or breaks in Bruch’s membrane that forms a barrier for growth of choroidal vessels under normal conditions (Georgalas et al. 2009). The present case report suggests anetoderma as a possible new risk factor for the development of subretinal neovascularization. A more detailed elucidation of the changes in elastic tissue in anetoderma and other connective tissue diseases may help understanding the pathophysiology of subretinal neovascularization in general.

Prolonged blockade of VEGF receptors does not damage retinal photoreceptors or ganglion cells

It has recently been reported that relatively short-term inhibition of vascular endothelial growth factor (VEGF) signaling can cause photoreceptor cell death, a potentially clinically important finding since VEGF blockade has become an important modality of treatment of ocular neovascularization and macular edema. However, in a set of studies in which we achieved extended and complete blockage of VEGF-induced vascular leakage through retinal expression of a VEGF binding protein, we did not observe any toxicity to retinal neurons. To follow-up on these apparently discrepant findings, we designed a set of experiments with the kinase inhibitor SU4312, which blocks phosphorylation of VEGF receptors, to look directly for evidence of VEGF inhibition-related retinal toxicity. Using transgenic mice with sustained expression of VEGF in photoreceptors, we determined that periocular injection of 3 microg of SU4312 every 5 days markedly suppressed subretinal neovascularization, indicating effective blockade of VEGF signaling. Wild-type mice given periocular injections of 5 microg of SU4312 every 5 days for up to 12 weeks showed normal scotopic and photopic electroretinograms (ERGs), no TUNEL stained cells in the retina, and no reduction in outer nuclear layer thickness. Incubation of cultured ganglion cells or retinal cultures containing photoreceptors with high doses of SU4312 did not reduce cell viability. These data suggest that blocking VEGF signaling in the retina for up to 12 weeks does not damage photoreceptors nor alter ERG function and should reassure patients who are receiving frequent injections of VEGF antagonists for choroidal and retinal vascular diseases.

Unilateral Idiopathic Macular Telangiectasia with Choroidal Neovascularization.

A 40-year-old man with decreasing visual acuity in his left eye over 1 year, diagnosed elsewhere as vein occlusion and treated unsuccessfully by systemic steroids was reported. Retrospective analysis of available previous imaging studies was undertaken, and a retrospective diagnosis of idiopathic macular telangiectasia (IMT) was made. Examination revealed subfoveal neovascularization and retinochoroidal anastomosis (RCA) in his left eye with macular edema and exudates surrounding it. The right eye was normal. Current fluorescein angiography (FA) confirmed the presence of choroidal neovascularization and RCA, and optical coherence tomography (OCT) demonstrated cystoid macular edema and subfoveal neovascularization.The patient was diagnosed with unilateral idiopathic macular telangiectasia complicated by subretinal neovascularization. The presences of a choroidal neovascularization process and an RCA have not, to our knowledge, been reported in this type of IMT.

The Complexity of Animal Model Generation for Complex DiseasesANIMAL MODEL GENERATION FOR COMPLEX DISEASES

Daniel M. Albert, MD, MS; Aneesh Neekhra, MD; Shoujian Wang, MD, PhD; Soesiawati R. Darjatmoko, BS; Christine M. Sorenson, PhD; Richard R. Dubielzig, DVM; Nader Sheibani, PhDObjectives To study the progressive changes of intense cyclic light–induced retinal degeneration and to determine whether it results in choroidal neovascularization (CNV).Methods Albino rats were exposed to 12 hours of 3000-lux cyclic light for 1, 3, or 6 months. Fundus examination, fundus photography, fluorescein and indocyanine green angiography, and optical coherence tomography were performed prior to euthanization. Light-exposed animals were euthanized after 1, 3, or 6 months for histopathological evaluation. Retinas were examined for the presence of 4-hydroxy-2-nonenal– and nitrotyrosine-modified proteins by immunofluorescence staining.Results Long-term intense cyclic light exposure resulted in retinal degeneration with loss of the outer segments of photoreceptors and approximately two-thirds of the outer nuclear layer as well as development of subretinal pigment epithelium neovascularization after 1 month. Almost the entire outer nuclear layer was absent with the presence of CNV, which penetrated the Bruch membrane and extended into the outer retina after 3 months. Absence of the outer nuclear layer, multiple foci of CNV, retinal pigment epithelial fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed after 6 months. All intense light–exposed animals showed an increased presence of 4-hydroxy-2-nonenal and nitrotyrosine staining. Optical coherence tomographic and angiographic studies confirmed retinal thinning and leakiness of the newly formed blood vessels.Conclusions Our results suggest that albino rats develop progressive stages of retinal degeneration and CNV after long-term intense cyclic light exposure, allowing the detailed study of the pathogenesis and treatment of age-related macular degeneration.Clinical Relevance The ability to study the progressive pathogenesis of age-related macular degeneration and CNV will provide detailed knowledge about the disease and aid in the development of target-specific therapy.

Development of Choroidal Neovascularization in Rats With Advanced Intense Cyclic Light–Induced Retinal Degeneration

To study the progressive changes of intense cyclic light-induced retinal degeneration and to determine whether it results in choroidal neovascularization (CNV). Albino rats were exposed to 12 hours of 3000-lux cyclic light for 1, 3, or 6 months. Fundus examination, fundus photography, fluorescein and indocyanine green angiography, and optical coherence tomography were performed prior to euthanization. Light-exposed animals were euthanized after 1, 3, or 6 months for histopathological evaluation. Retinas were examined for the presence of 4-hydroxy-2-nonenal- and nitrotyrosine-modified proteins by immunofluorescence staining. Long-term intense cyclic light exposure resulted in retinal degeneration with loss of the outer segments of photoreceptors and approximately two-thirds of the outer nuclear layer as well as development of subretinal pigment epithelium neovascularization after 1 month. Almost the entire outer nuclear layer was absent with the presence of CNV, which penetrated the Bruch membrane and extended into the outer retina after 3 months. Absence of the outer nuclear layer, multiple foci of CNV, retinal pigment epithelial fibrous metaplasia, and connective tissue bands containing blood vessels extending into the retina were observed after 6 months. All intense light-exposed animals showed an increased presence of 4-hydroxy-2-nonenal and nitrotyrosine staining. Optical coherence tomographic and angiographic studies confirmed retinal thinning and leakiness of the newly formed blood vessels. Our results suggest that albino rats develop progressive stages of retinal degeneration and CNV after long-term intense cyclic light exposure, allowing the detailed study of the pathogenesis and treatment of age-related macular degeneration. The ability to study the progressive pathogenesis of age-related macular degeneration and CNV will provide detailed knowledge about the disease and aid in the development of target-specific therapy.

Idiopathic juxtafoveolar retinal telangiectasis: A current review

Idiopathic juxtafoveolar retinal telangiectasis (IJFT), also known as parafoveal telangiectasis or idiopathic macular telangiectasia, refers to a heterogeneous group of well-recognized clinical entities characterized by telangiectatic alterations of the juxtafoveolar capillary network of one or both eyes, but which differ in appearance, presumed pathogenesis, and management strategies. Classically, three groups of IJFT are identified. Group I is unilateral easily visible telangiectasis occurring predominantly in males, and causing visual loss as a result of macular edema. Group II, the most common, is bilateral occurring in both middle-aged men and women, and presenting with telangiectasis that is more difficult to detect on biomicroscopy, but with characteristic and diagnostic angiographic and optical coherence tomography features. Vision loss is due to retinal atrophy, not exudation, and subretinal neovascularization is common. Group III is very rare characterized predominantly by progressive obliteration of the perifoveal capillary network, occurring usually in association with a medical or neurologic disease. This paper presents a current review of juxtafoveolar retinal telangiectasis, reviewing the classification of these entities and focusing primarily on the two most common types encountered in clinical practice, i.e., groups I and II, describing their clinical features, histopathology, natural history, complications, latest results from imaging modalities and functional studies, differential diagnosis, and treatment modalities.