CHOROIDAL NEOVASCULARIZATION IN CAUCASIAN PATIENTS WITH LONGSTANDING CENTRAL SEROUS CHORIORETINOPATHY.

PURPOSE: To report the frequency of choroidal neovascularization (CNV) in Caucasian patients with chronic central serous chorioretinopathy (CSC). METHODS: Retrospective consecutive series of 272 eyes (136 patients) who were diagnosed as having chronic CSC based on clinical and multimodal fundus imaging findings and documented disease activity for at least 6 months. The CNVs were mainly determined by indocyanine-green angiography. RESULTS: Patients were evaluated and followed for a maximum of 6 years, with an average follow-up of 14 ± 12 months. Distinct CNV was identified in 41 eyes (34 patients). Based on fluorescein angiography, 37 eyes showed occult with no classic CNV, 3 eyes showed predominantly classic and 1 eye had a disciform CNV. Furthermore, indocyanine-green angiography revealed polypoidal choroidal vasculopathy lesions, in 27 of the 37 eyes, classified as occult CNV on fluorescein angiography. In total, 17.6% of our patients with chronic CSC were found to have CNV that upon indocyanine-green angiography were recognized as being polypoidal choroidal vasculopathy. CONCLUSION: In our series of Caucasian patients, we found a significant correlation between chronic CSC and CNV, in which the majority of patients with CNV were found to have polypoidal choroidal vasculopathy. Our findings suggest that indocyanine-green angiography is an indispensable tool in the investigation of chronic CSC.

Peripapillary choroidal neovascularization in best disease.

BACKGROUND: Best disease is an autosomal dominant retinal dystrophy with a variable phenotypic expression. Clinically, it is characterized by a vitelliform lesion in the macula because of the deposition of yellow material in a dome-shaped configuration, believed to be lipofuscin that accumulates within and beneath the retinal pigment epithelium. Best disease is occasionally complicated by the development of choroidal neovascularization (CNV), which typically occurs in the macula. We report a case of peripapillary CNV in Best disease. METHODS: Interventional case report. RESULTS: A 12-year-old boy who was previously diagnosed with Best disease was treated with reduced fluence photodynamic therapy for subfoveal CNV in the right eye. After 2 months, he presented with peripapillary CNV in the left eye, which was treated with repeated sessions of reduced fluence photodynamic therapy. CONCLUSION: Ophthalmologists must be aware that peripapillary CNV may occasionally complicate Best disease and can be successfully treated with photodynamic therapy.

Three major loci involved in age-related macular degeneration are also associated with polypoidal choroidal vasculopathy.

PURPOSE: To investigate the frequency of variants in 3 major age-related macular degeneration (AMD)-associated loci in patients of European-American descent with polypoidal choroidal vasculopathy (PCV). DESIGN: Cross-sectional, case-control association study. PARTICIPANTS: Fifty-five patients with PCV, 368 patients with advanced AMD, and 368 age-matched and ethnically matched unaffected controls of European-American descent. METHODS: Association analysis of allele and genotype frequencies, determined by TaqMan assays, was performed for the following haplotype-tagging single nucleotide polymorphisms (htSNPs): risk alleles in the complement factor H (CFH) gene (Y402H and IVS14) in the ARMS2/HTRA1 locus on 10q26 (A69S) and protective alleles in CFH (IVS1 and IVS6) and in the complement factor B/complement component C2 (CFB/C2) locus (IVS10 and H9L). MAIN OUTCOME MEASURES: Allele and genotype frequencies of the htSNPs in the CFH, CFB/C2, and ARMS2/HTRA1 loci. RESULTS: Four AMD-associated haplotype-tagging alleles (rs547154, rs1061170, rs1410996, rs10490924) in the 3 major loci, CFH, CFB/C2, and ARMS2/HTRA1, also were statistically significantly associated with the PCV phenotype (P<0.05). Three other alleles from the same loci (rs4151667, rs529825, rs3766404) showed a trend toward association (P<0.2) but did not reach statistical significance, possibly because of the combined effects of a relatively small sample size and low minor allele frequency in the screened populations. CONCLUSIONS: The PCV phenotype in Caucasian patients is associated with the major alleles/genotypes in the AMD-associated loci, suggesting that PCV and AMD are genetically similar in the tested loci.

Multimodal fundus imaging in Best vitelliform macular dystrophy.

BACKGROUND: Best vitelliform macular dystrophy (BVMD) is a rare autosomal dominant retinal disease of highly variable phenotypic expression. Interpretations of disease mechanisms based on histopathology, electrophysiology, genetic analysis, and retinal imaging are somewhat discordant in fundamental issues such as the location and extension of primary retinal changes. Herein we describe the morphological macular features in patients with BVMD undergoing simultaneous multimodal fundus imaging and compare to those of normal age-matched subjects. METHODS: Comparative study including seven patients with BVMD (14 eyes) and seven age-matched healthy subjects (14 eyes). All participants were submitted to complete ophthalmological examination, fundus photography, and standardized multimodal fundus imaging protocol including Fourier-domain optical coherence tomography (Fd-OCT) combined with near-infrared reflectance and blue-light fundus autofluorescence (FAF). RESULTS: In two eyes in the "subclinical" stage, Fd-OCT revealed thickening of the middle highly reflective layer (HRL) localized between the photoreceptors' inner/outer segments junction (inner-HRL) and RPE/Bruch's membrane reflective complex (outer-HRL) throughout the macula. In one eye in the "vitelliform" stage, a homogeneous hyper-reflective material on Fd-OCT was observed between the middle-HRL and outer-HRL; this material presented increased fluorescence on FAF. The outer nuclear layer (ONL) was thinned in the central macula and subretinal fluid was not identified in these earlier disease stages. In patients of "pseudohypopyon" (two eyes), "vitelliruptive" (eight eyes) and "atrophic" (one eye) stages, Fd-OCT revealed a variety of changes in the middle- and inner-HRLs and thinning of ONL. These changes were found to be associated with the level of visual acuity observed. Thickening of the middle-HRL was observed beyond the limits of the clinically evident macular lesion in all eyes. CONCLUSIONS: Multimodal fundus imaging demonstrated thickening of the reflective layer corresponding to the photoreceptors' outer segments throughout the macula with no subretinal fluid accumulation as the earliest detectable feature in BVMD. Changes detected in the photoreceptors' reflective layers (middle- and inner- HRLs) and ONL thinning seemed to be progressive with direct implications for the level of visual acuity impairment observed among the different stages of the disease.

Unusual Loop-Like Vessel Formation After Intravitreal Ranibizumab Injections in AMD.

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.

Bilateral choroidal neovascularization in birdshot retinochoroidopathy treated with intravitreal injections of triamcinolone and bevacizumab.

PURPOSE: To describe a patient with birdshot retinochoroidopathy (BRC) with bilateral choroidal neovascularization (CNV) who was treated with intravitreal injection of bevacizumab and antiinflammatory medications. METHOD: Interventional case report. PATIENT: A 35-year-old woman with bilateral CNV associated with BRC. RESULTS: The patient was treated with intravitreal injection of triamcinolone, photodynamic therapy, and intravitreal injection of bevacizumab in one eye, while the fellow eye was treated with intravitreal injection of triamcinolone. Immunosuppressive therapy was performed in the course of the treatment. Not only did the neovascularization respond, but the birdshot lesions vanished as well. DISCUSSION: BRC can have secondary CNV that, as in the current case, responds favorably to treatment. We serendipitously observed regression of the choroidal inflammatory lesions with intravitreal injection of triamcinolone.

Analysis of major alleles associated with age-related macular degeneration in patients with multifocal choroiditis: strong association with complement factor H.

OBJECTIVE: To analyze the frequency of major age-related macular degeneration (AMD)-associated alleles in patients with multifocal choroiditis (MFC). METHODS: A cohort of 48 patients with MFC was compared with previously characterized cohorts of patients with advanced AMD (368 samples) and matched unaffected controls (368 samples). Allele and genotype frequencies of single nucleotide polymorphisms for the following AMD-associated alleles were evaluated: risk alleles in complement factor H (CFH) gene (Y402H and IVS14) and LOC387715/HTRA1 gene on 10q26 (A69S) and protective alleles in CFH (IVS1, IVS6, and delCFHR1-3) and complement factor B loci (H9L and R32Q). RESULTS: Frequencies of all major AMD-associated alleles in the CFH locus indicate a strong, statistically significant association of CFH gene single nucleotide polymorphisms and MFC. However, the same analysis for the single nucleotide polymorphisms in complement factor B and 10q26 loci matched the results in the control group. CONCLUSIONS: Like AMD, the MFC phenotype is strongly associated with the major alleles/haplotypes in the CFH locus. Clinical Relevance We report compelling evidence of a strong association between CFH polymorphisms and MFC, which contributes to the understanding of MFC pathogenesis and suggests new potential therapeutic targets.

Bilateral choroidal osteomas with polypoidal choroidal vasculopathy.

BACKGROUND: A choroidal osteoma is a benign osseous tumor typically arising in the juxtapapillary or peripapillary area. The major cause of visual loss is secondary to the development of a subretinal neovascular membrane. The pattern of neovascularization that develops with osteomas has been typically described as classic choroidal neovascularization (CNV). METHODS: Interventional case report. RESULTS: A case of bilateral polypoidal choroidal neovascularization (PCV) occurring with bilateral choroidal osteomas is described in a 55-year-old Japanese woman. To our knowledge, this variant form of vasogenesis has not previously been described in association with this tumor. Clinical, angiographic, and optical coherence tomographic features are discussed. Subretinal hemorrhage in the left eye from polypoidal neovascularization in the macula was successfully treated with photodynamic therapy. CONCLUSIONS: The association between choroidal osteoma and PCV may have a better prognosis than that with classic CNV. Indocyanine green angiography is a useful tool in characterizing the nature of the neovascularization.

Central retinal vein occlusion case-control study.

PURPOSE: To investigate risk factors for central retinal vein occlusion (CRVO). DESIGN: Retrospective case-control study. METHODS: Consecutive patients with CRVO examined from July 1, 2005 through July 31, 2006 were compared with an historical gender- and age-matched control group of patients with ocular problems other than vascular occlusive disease from the same referral practice. Risk factors for CRVO were evaluated. RESULTS: The 144 patients in the CRVO group, 87 males and 57 females, had a mean age of 69.6 years (+/-13.6 years). CRVO was associated with hypertension (P < .001), diabetes mellitus (P = .047), glaucoma (P < .001), atrial fibrillation (P = .036), angiotensin-converting enzyme inhibitor use (P = .022), aspirin use (P < .001), and warfarin use (P = .011) by univariate analyses. Postmenopausal estrogen use was more common among women in the control group (P = .029). Multivariate logistic regression found the independent predictors for CRVO to be: glaucoma (adjusted odds ratio [OR], 4.75; P < .001), aspirin use (adjusted OR, 2.66; P = .001), and warfarin use (adjusted OR, 3.34; P = .005). CONCLUSIONS: We found many of the same risk factors previously identified for CRVO by other studies, but we identified both aspirin and warfarin use to be independent risk factors for CRVO. Although these findings suggest the vasculopathic and prothrombotic risks in some patients may not be addressed adequately by antithrombotic therapy, they also suggest that the pathogenesis of CRVO may be more complicated than just the development of a primary thrombus within the vein.

Early bevacizumab treatment of central retinal vein occlusion.

PURPOSE: To evaluate the change in visual acuity and retinal appearance in patients after early initiation of intravitreal bevacizumab treatment for central retinal vein occlusion (CRVO). DESIGN: Retrospective, interventional case series. METHODS: Patients with CRVO of fewer than three months' duration receiving intravitreal bevacizumab as primary treatment were evaluated. Patients received an intravitreal 1.25 mg (0.05 ml) bevacizumab injection. Changes in visual acuity, central macular thickness, venous tortuosity and diameter, and optic disk edema were noted. RESULTS: Six eyes of five consecutive patients with CRVO treated with intravitreal bevacizumab injection were reviewed retrospectively. The patients did not have other ocular conditions that could have compromised visual acuity. The mean baseline visual acuity was 20/428 (logarithm of the minimum angle of resolution [logMAR] units, 1.33). The mean follow-up period was 12 months (range, seven to 15 months), and the number of bevacizumab injections ranged from four to 10. The patients showed a statistically significant decrease in optic nerve head swelling, venous tortuosity, and venous diameter, with the largest proportion of change occurring within one month of the first bevacizumab injection. The mean visual acuity at last follow-up was 20/53 (logMAR units, 0.42; P = .035, as compared with baseline). In no patient did collateral vessels at the optic nerve head develop. CONCLUSIONS: The patients experienced a dramatic improvement in the visual acuity and clinical fundus appearance, without collateral vessel formation. These findings are difficult to explain with current theories of the pathophysiologic features of CRVO. These findings also suggest early initiation of anti-vascular endothelial growth factor (VEGF) treatment should be studied in a larger trial for CRVO.

Rebound macular edema following bevacizumab (Avastin) therapy for retinal venous occlusive disease.

BACKGROUND: Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor (VEGF), has been given via intravitreal injection as an off-label therapy for both neovascular age-related macular degeneration and for macular edema secondary to retinal vascular disease. The authors describe three patients with macular edema secondary to retinal venous occlusion whose edema initially responded to intravitreal bevacizumab but subsequently recurred in excess of that observed before treatment. METHODS: This is a retrospective case series of three patients with macular edema secondary to retinal vein occlusion treated with intravitreal bevacizumab. RESULTS: In all three patients, the rebound retinal edema observed was more pronounced than that present before treatment. CONCLUSION: These cases suggest a potential limitation of using relatively short-acting VEGF antagonists in retinal vascular disease of a chronic nature. Frequent repeated injections may be required to prevent a rebound effect with no clearly defined endpoint. Until the long-term safety of multiple injections of these agents is established, the authors recommend caution in using this treatment strategy.