Faculty Bibliography

BACKGROUND: It is known that choroidal neovascularization (CNV) in age-related macular degeneration (ARMD) may erode through the retinal pigment epithelium, infiltrate the neurosensory retina, and communicate with the retinal circulation in what has been referred to as a retinal-choroidal anastomosis (RCA). This is extremely common in the end stage of disciform disease. In recent years, the reverse also seems to be possible, as angiomatous proliferation originates from the retina and extends posteriorly into the subretinal space, eventually communicating in some cases with choroidal new vessels. This form of neovascular ARMD, termed retinal angiomatous proliferation (RAP) in this article, can be confused with CNV. Purpose: The purpose of this article is 1) to review the clinical and angiographic characteristics of a series of patients with RAP and 2) to propose a theoretical sequence of events that accounts for the neovascularized process. METHODS: In this retrospective clinical and angiographic analysis, 143 eyes with RAP (108 patients) were reviewed and classified based on their vasogenic nature and course. Clinical biomicroscopic examination, fluorescein angiography, and indocyanine green angiography were used to evaluate patients. RESULTS: The results of this series suggest that angiomatous proliferation within the retina is the first manifestation of the vasogenic process in this form of neovascular ARMD. Dilated retinal vessels and pre-, intra-, and subretinal hemorrhages and exudate evolve, surrounding the angiomatous proliferation as the process extends into the deep retina and subretinal space. One or more dilated compensatory retinal vessels perfuse and drain the neovascularization, sometimes forming a retinal-retinal anastomosis. Fluorescein angiography in these patients usually revealed indistinct staining simulating occult CNV. Indocyanine green angiography was useful to make an accurate diagnosis in most cases. It revealed a focal area of intense hyperfluorescence corresponding to the neovascularization ("hot spot") and other characteristic findings. Based on understanding of the nature and progression of the neovascularized process, patients with RAP were classified into three vasogenic stages. Stage I involved proliferation of intraretinal capillaries originating from the deep retinal complex (intraretinal neovascularization [IRN]). Stage II was determined by growth of the retinal vessels into the subretinal space (subretinal neovascularization [SRN]). Stage III occurred when CNV could clearly be determined clinically or angiographically. A vascularized pigment epithelial detachment and RCA were inconsistent features of this stage. CONCLUSIONS: Retinal angiomatous proliferation appears to be a distinct subgroup of neovascular ARMD. It may present in one of three vasogenic stages: IRN, SRN, or CNV. Whereas ICG angiography is helpful in diagnosing RAP and in documenting the stage of the neovascularized process, it is frequently difficult to determine the precise nature and location of the new vessel formation. It is important for clinicians to recognize the vasogenic potential and the associated manifestations of this peculiar form of neovascular ARMD so that a proper diagnosis can be made, and when possible, an appropriate management administered.

PURPOSE: To study the effects of photodynamic therapy using verteporfin in the treatment of patients with subfoveal polypoidal choroidal vasculopathy (PCV). METHODS: A retrospective chart review of 16 consecutive patients with subfoveal PCV treated with photodynamic therapy using verteporfin was performed. RESULTS: The mean age of the patients involved was 70.5 years. The mean follow-up time was 12 months. The visual acuity improved in 9 (56.3 %), remained the same in 5 (31.3 %), and decreased in 2 (12.5 %). The mean change in visual acuity was an improvement of 2.38 lines, a difference that was highly significant (P = 0.004). The change in visual acuity was negatively correlated with increasing age. The final visual acuity was positively correlated with initial acuity and negatively correlated with age. These results were confirmed by multiple linear regression. No patient had any lasting complication from the treatment. CONCLUSIONS: Subfoveal PCV has no proven method of treatment. Although the follow-up time and the number of patients in this pilot study were limited, the encouraging results and lack of complications suggest that further study is indicated.

PURPOSE: To evaluate long-term effectiveness and safety of intravitreal injection of ranibizumab as a potential treatment for decreased visual acuity secondary to central retinal vein occlusion. METHODS: In this prospective interventional case series, patients with central retinal vein occlusion were administered intravitreal ranibizumab 0.5 mg at baseline and monthly for 2 additional doses. Thereafter, the patients were given additional ranibizumab if they had macular edema by optical coherence tomography, leakage during fluorescein angiography, or any intraretinal hemorrhage. RESULTS: There were 35 eyes of 35 patients who at baseline had a mean visual acuity of 44.2 Early Treatment Diabetic Retinopathy Study letters and a mean central macular thickness of 638 mum. At 12 months, mean visual acuity of 32 eyes improved by 16.5 letters and macular thickness decreased to 164 mum (P < 0.001 vs. baseline for each). At 24 months, mean visual acuity of 24 eyes improved by 17.8 letters and macular thickness was 263 mum (P < 0.001 vs. baseline for each). Patients received an average of 10.2 injections during the first year and 6.6 injections during the second year. No cases of endophthalmitis, retinal detachment, or neovascularization were observed. CONCLUSION: Intravitreal ranibizumab caused a significant improvement in visual acuity and central retinal thickness, which persisted for up to 2 years with minimal side effects

The authors observed an unusual closed loop-like vessel formation in the macula and describe its regression caused by the heterogenous treatment effects of intravitreal ranibizumab injections in an eye with exudative age-related macular degeneration associated with multiple retinochoroidal anastomoses

PURPOSE: To determine the safety, tolerability, maximum tolerated dose, and bioactivity of an intravitreal injection of vascular endothelial growth factor (VEGF) Trap-Eye, a fusion protein of binding domains from human VEGF receptors 1 and 2 with human immunoglobulin-G Fc that binds VEGF family members, in patients with neovascular age-related macular degeneration (AMD). DESIGN: Dose-escalation, multicenter, interventional clinical trial. PARTICIPANTS: Twenty-one patients (13 female, 8 male) with neovascular AMD (NVAMD) and lesions </=12 disc areas in size and >/=50% active choroidal neovascularization (CNV) with best-corrected visual acuity (BCVA) </=20/40 received a single intraocular injection of 0.05 mg (n = 3), 0.15 mg (n = 3), 0.5 mg (n = 3), 1 mg (n = 6), 2 mg (n = 3), or 4 mg (n = 3) of VEGF Trap-Eye. METHODS: Safety assessments included eye examinations, vital signs, and laboratory tests. Measures of bioactivity included changes from baseline in BCVA, optical coherence tomography (OCT), and fluorescein angiography. The primary end point was 6 weeks and patients were followed up for 12 weeks. MAIN OUTCOME MEASURE: Safety assessments. RESULTS: There were no serious adverse events and no identifiable intraocular inflammation. The mean decrease in excess foveal thickness for all patients was 104.5 mum at 6 weeks, and the mean increase in visual acuity was 4.43 letters. In the 2 highest dose groups combined (2 and 4 mg), the mean increase in BCVA was 13.5 letters, with 3 of 6 patients demonstrating improvement of >/=3 lines and 3 patients requiring no adjunctive treatment of any type for 12 weeks. Some showed elimination of fluorescein leakage and reduction in area of CNV. CONCLUSIONS: Intravitreal injection of up to 4 mg of VEGF Trap-Eye in patients with NVAMD was well tolerated with no evidence of ocular inflammation. Although the number of patients in each cohort was small, there was evidence of bioactivity, because several patients, especially those receiving 2 or 4 mg of VEGF Trap-Eye, showed substantial improvement in BCVA associated with reductions in foveal thickness. Phase III trials to investigate the efficacy of intraocular VEGF Trap-Eye in patients with NVAMD are under way. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references

PURPOSE: To explore the incidence of complications after bilateral same-day intravitreal injections of antivascular endothelial growth factor pharmacotherapies in this retrospective interventional case series. METHODS: An electronic review of billing records was performed to identify all bilateral same-day intravitreal antivascular endothelial growth factor injections performed within a single group retina practice between January 6, 2006 and June 1, 2009. The charts were reviewed to identify the complications of endophthalmitis, intraocular inflammation, retinal tear, and retinal detachment. RESULTS: A total of 1,534 bilateral intravitreal injections (326 bevacizumab and 1,208 ranibizumab: 3,068 injections total) were performed in 367 patients. Three complications were identified. Two cases of unilateral culture-proven endophthalmitis occurred after bilateral intravitreal ranibizumab, and one case of unilateral acute intraocular inflammation occurred after bilateral intravitreal bevacizumab. In all three of these eyes, visual acuity returned to its preinjection level. No cases of retinal tear or retinal detachment were identified. The incidence of culture-proven endophthalmitis was 0.065%, and the incidence of acute intraocular inflammation was 0.033%. CONCLUSION: The complication rates after bilateral same-day intravitreal antivascular endothelial growth factor injections seem to be similar to those after unilateral injections. Severe acute intraocular inflammation can occur unilaterally after same-day bilateral injections of bevacizumab

PURPOSE: To measure macular choroidal thickness (CT) in highly myopic eyes using enhanced depth imaging optical coherence tomography (OCT). DESIGN: Retrospective, observational case series. METHODS: Enhanced depth imaging OCT images were obtained in highly myopic eyes (> or =6 diopters [D]). Images of CT were obtained by positioning a spectral-domain OCT device close enough to the eye to acquire an inverted image. CT was measured from the outer border of the retinal pigment epithelium to the inner scleral border at 1000-mum intervals of a horizontal section from 3 mm temporal to the fovea to 3 mm nasal to the fovea. Statistical analysis was performed to evaluate CT at each location and to correlate CT with age and refractive error. RESULTS: The mean age of the 31 patients (55 eyes) was 59.7 years (+/- 17.6 years; range, 24 to 90 years), and the mean refractive error was -11.9 D (+/- 3.7 D). The mean subfoveal CT was 93.2 microm (+/- 62.5 microm) and was correlated negatively with age (P = .006), refractive error (P < .001), and history of choroidal neovascularization (P = .013). Regression analysis suggested that subfoveal CT decreased by 12.7 mum for each decade of life and by 8.7 microm for each D of myopia. CONCLUSIONS: The choroid in highly myopic eyes is very thin and undergoes further thinning with increasing age and degree of myopia. Abnormalities of the choroid may play a role in the pathogenesis of myopic degeneration

PURPOSE: To assess outcomes for patients with choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) treated with verteporfin photodynamic therapy (PDT) and bevacizumab. DESIGN: Retrospective, case series database study (registry). PARTICIPANTS: We included 1196 patients with CNV due to AMD who received > or =1 combination treatment of 1.25 mg intravitreal bevacizumab within 14 days of verteporfin PDT. METHODS: Retrospective analysis of baseline data with ongoing follow-up. Physicians from 45 clinical centers entered patient data at baseline and follow-up examinations, including subsequent treatments, into a secure, Web-accessed database. Snellen visual acuity (VA) was converted to logarithm of the minimum angle of resolution (logMAR) for statistical analyses. MAIN OUTCOME MEASURES: Change from baseline in VA and retreatment rates of any therapy after the initial combination treatment. RESULTS: Of 1196 patients, 1073 patients had > or =6 months of follow-up. For these 1073 patients, mean baseline VA was 0.967 logMAR (approximate Snellen 20/185) and 56.3% of patients (604/1073) were treatment naive. After their baseline combination treatment, patients received a mean of 0.6 additional verteporfin PDT retreatments and 2.0 bevacizumab retreatments over a mean follow-up period of 15.0 months. By 12 months, 82% of patients (578/701) had stable or improved vision (loss of <3 lines or a gain in VA), 36% (255/701) improved by > or =3 lines, and 17% (121/701) improved by > or =6 lines. By 12 months, patients gained approximately 1.2 lines (6 letters) of VA from baseline. Patients who were treatment naive gained significantly more VA by month 12 (+8.4 letters) compared with those who had been previously treated (+2.4 letters; P<0.01). Most serious adverse events (26/30) were judged by investigators as not related to any study treatment, although 3 ocular events were judged related to bevacizumab alone, and 1 ocular event was judged related to both bevacizumab and PDT. CONCLUSIONS: Combination therapy with PDT and bevacizumab led to vision benefit for most patients, particularly those who were treatment naive at baseline. The number of retreatments was lower than published reports with either treatment delivered as monotherapy. Randomized clinical trials are underway to confirm these findings

PURPOSE: To evaluate intravitreal injection of ranibizumab as a potential treatment for decreased visual acuity (VA) secondary to central retinal vein occlusion (CRVO). DESIGN: Prospective, interventional case series. METHODS: Patients with CRVO prospectively recruited from a practice were administered intravitreal ranibizumab 0.5 mg (Lucentis; Genentech Inc, South San Francisco, California, USA) at baseline and monthly for two additional doses. The patients were given additional ranibizumab if they had macular edema as determined by optical coherence tomography or any new intraretinal hemorrhage. Patients were evaluated for number of required injections, side effects, changes in VA, and macular thickness. RESULTS: There were 20 eyes of 20 patients who at baseline had a mean age of 72.1 years, a mean VA of 45.8 Early Treatment of Diabetic Retinopathy letters, and a mean central macular thickness of 574.6 microm. Of the 20 eyes, five previously had received intravitreal triamcinolone and 11 had received intravitreal bevacizumab (Avastin; Genentech Inc). At 12 months of follow-up, the mean VA improved to 64.3 letters and the central macular thickness decreased to 186 microm (both different than baseline values; P < .001) using a mean of 8.5 injections. The change in macular thickness was not correlated with the change in VA. In one patient with a history of transient ischemic attack, an ischemic stroke developed but no sequela resulted. In another patient, vitreomacular traction developed, but the patient had improved acuity as compared with baseline. There were no infections, retinal tears, or detachments. CONCLUSIONS: Intravitreal ranibizumab used over a period of one year improved mean VA, with low rates of adverse events, in patients with CRVO

OBJECTIVE: To report the results of intravitreous bevacizumab (Avastin) treatment for choroidal neovascularization (CNV) from causes other than age-related macular degeneration (AMD). METHODS: We performed a retrospective analysis of eyes that received intravitreous bevacizumab, 1.25 mg, for subfoveal non-AMD CNV at a referral-based retinal practice. Repeated treatment with intravitreous bevacizumab occurred if there were signs of persistent or recurrent exudation. The main outcome measure was visual acuity (VA). RESULTS: The study included 39 eyes of 36 patients with subfoveal CNV secondary to multifocal choroiditis (n = 12), angioid streaks (n = 11), myopic degeneration (n = 10), idiopathic disease (n = 4), or other disease (n = 2). The median baseline VA was 20/60 (logMAR, 0.48). The mean follow-up was 58.8 weeks, and the mean number of injections per eye was 3.4. After 3-month follow-up, the median VA was 20/30 (logMAR, 0.18) (P = .004 vs baseline). At last follow-up, the median VA was 20/40 (logMAR, 0.30). This remained an improvement compared with baseline (P < .02) but was worse than 3-month follow-up (P < .03). There was no correlation between underlying diagnosis and VA change during follow-up. CONCLUSION: Subfoveal CNV secondary to non-AMD causes treated with intravitreous bevacizumab responded favorably and similarly, despite varying underlying etiologies