Early effects of dexamethasone and anti-VEGF therapy in an inflammatory corneal neovascularization model.

Inflammatory angiogenesis is the pathogenic mechanism of various sight-threatening eye diseases, among them corneal neovascularization. Current treatment options include steroids which have undesirable side effects, or anti-VEGF which has only limited efficacy. In an inflammatory environment, however, angiogenesis can be stimulated by numerous factors not directly targeted by anti-VEGF therapy. The aim of this study was to induce corneal inflammation leading to angiogenesis, and investigate the early, differential effects of steroid and anti-VEGF therapy at the cellular, tissue, and gene expression levels. Fifty-two Wistar rats received a single intrastromal corneal suture to induce a controlled inflammatory angiogenic response. Rats were subsequently treated with dexamethasone, rat specific anti-VEGF, or goat IgG (control), topically 4 times daily for 7 days. In vivo confocal microscopy of the cornea was performed longitudinally from 5 h up to 7 d to investigate morphology at the cellular and tissue-level. In vivo photographic vessel analysis and immunohistochemistry were also performed. RT-PCR for VEGF-A, FGF-2, IL-6, TNF-α, CXCL2, CCL2, CCL3 and DLL4 was performed at 24 h, and for VEGF-A, IL-6, TNF-α, FGF-2, CXCL2, CCL2, and CCL3 at 7 days. Early infiltration of CD11b + myeloid cells into the cornea at 5 h post-suture was delayed by both treatments relative to controls; however neither treatment was able to suppress accumulation of myeloid cells at day 2 or 7. Limbal vessel dilation was inhibited at 5 h by both treatments, but only dexamethasone showed sustained effect until day 2. Early macrophage recruitment was also suppressed by dexamethasone (but not by anti-VEGF) until day 2. Dexamethasone furthermore suppressed corneal neovascularization at day 7 by over 90%, whereas suppression by anti-VEGF was 14%. Despite differential suppression of vessel dilation, macrophage recruitment, and vascular invasion, anti-VEGF and dexamethasone both down-regulated VEGF-A and IL-6 expression at 24 h with sustained effect to 7 d. They also both down regulated FGF-2 and TNF-α at 24 h and CCL2 at 7 d. In conclusion, anti-angiogenic treatments influence early, pre-angiogenic tissue activity such as limbal vessel dilation, inflammatory cell infiltration of the stroma, and macrophage recruitment. Importantly, the differential effects of steroids and anti-VEGF treatment in suppressing neovascular growth could not be attributed to differential inhibition of several major angiogenic and inflammatory factors in the early pre-sprouting phase, including IL-6, VEGF-A, FGF-2, TNF-α, CCL2, CCL3, CXCL2, or DLL4.

Acute exudative polymorphous vitelliform maculopathy in a young woman: presymptomatic findings and 21-month follow-up.

PURPOSE: To describe ocular findings before and after the diagnosis of acute exudative polymorphous vitelliform maculopathy, in an otherwise healthy 28-year-old woman. METHODS: Case report with 21-months of follow-up. Fundus photography, optical coherence tomography, fluorescein angiography, indocyanine green angiography, and autofluorescence were used for imaging the retina. To examine retinal function, full-field electroretinogram, multifocal electroretinogram, electrooculography, and dark adaptometry were performed. Genetic analysis for mutations associated with Best disease was done. RESULTS: In the asymptomatic patient before diagnosis, white-yellow, drusen-like, subretinal depositions were found in both eyes. A few months later, the patient developed bilateral visual disturbances. Retinal examination at the acute phase revealed a characteristic pattern of multifocal white-yellow subretinal lesions in both posterior poles, imaged by ophthalmoscopy, fluorescein angiography, indocyanine green angiography, and optical coherence tomography. Additionally, electrooculography and dark adaptometry were abnormal. Full-field electroretinogram was normal, but multifocal electroretinogram revealed central depression of peak amplitudes. During the 21-month follow-up without any treatment, visual acuity recovered, electrooculography and dark adaptometry normalized, and the patient experienced one episode of relapse. Genetic studies excluded mutations in the bestrophin gene (BEST1). CONCLUSION: Acute exudative polymorphous vitelliform maculopathy is still a condition of unknown origin, primarily affecting the pigment epithelium. Earlier reports have discussed whether the condition is inherited or acquired. In this report, the presymptomatic retinal findings in acute exudative polymorphous vitelliform maculopathy are described for the first time, indicating that a condition may be associated with primarily affected retinal pigment epithelium.

Significant improvements in near vision, reading speed, central visual field and related quality of life after ranibizumab treatment of wet age-related macular degeneration.

PURPOSE: To investigate the effects on near visual acuity, reading speed, central visual field and related quality of life of ranibizumab treatment of wet age-related macular degeneration (AMD). METHODS: The study was a prospective, non-comparative consecutive case series, followed for 3 months and investigator-driven. Thirty eyes of 30 patients with wet AMD were included, mean age 75 years (range 69-95 years). In addition to a full ophthalmological examination--including best-corrected visual acuity (BCVA; Early Treatment Diabetic Research Study chart), fundus biomicroscopy, fundus photography, fluorescein angiography, indocyanine green angiography (occult cases) and ocular coherence tomography--near visual acuity, reading speed, central visual field and quality of life for related activities were also investigated at baseline and at 3 months after ranibizumab treatment. RESULTS: Mean BCVA increased from 62 +/- 11 to 66 +/- 14 letters at 3 months (7%; p = 0.018). Near vision improved from 9 +/- 5 to 6 +/- 3 points (33%; p = 0.0006) and reading speed increased from 59 +/- 40 to 85 +/- 50 words/min (44%; p < 0.0001). The mean deviation from normal of the visual field improved from -9 +/- 7 to -6 +/- 5 dB (33%; p < 0.0001). Quality of life improved for distance activities from 54 +/- 28 to 63 +/- 28 points (17%; p < 0.0001) but significantly (p = 0.024) more for near activities, from 49 +/- 26 to 63 +/- 26 points (29%; p < 0.0001). Reading newspaper text in the group in which the better eye was treated showed the highest increase in quality of life score of all: 116%. CONCLUSION: The increase in BCVA after ranibizumab treatment is well established. The present study also showed significant improvements in other important visual qualities, such as near visual acuity, reading speed, central visual field and several activities influencing quality of life. The improvement was greater for near activities than for distance activities. Therefore, the beneficial effects of ranibizumab treatment shown here are more extensive than those reported previously.