Systemic complement inhibition with eculizumab for geographic atrophy in age-related macular degeneration: the COMPLETE study.

PURPOSE: To evaluate the effect of eculizumab, a systemic inhibitor of complement component (C5), on the growth of geographic atrophy (GA) in patients with age-related macular degeneration (AMD). DESIGN: Prospective, double-masked, randomized clinical trial. PARTICIPANTS: Patients with GA measuring from 1.25 to 18 mm(2) based on spectral-domain optical coherence tomography imaging. METHODS: Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 6 months. In the eculizumab treatment arm, the first 10 patients received a low-dose regimen of 600 mg weekly for 4 weeks followed by 900 mg every 2 weeks until week 24, and the next 10 patients received a high-dose regimen of 900 mg weekly for 4 weeks followed by 1200 mg every 2 weeks until week 24. The placebo group was infused with saline. Patients were observed off treatment for an additional 26 weeks. Both normal-luminance and low-luminance visual acuities were measured throughout the study, and the low-luminance deficits were calculated as the difference between the letter scores. MAIN OUTCOME MEASURES: Change in area of GA at 26 weeks. RESULTS: Thirty eyes of 30 patients were enrolled. Eighteen fellow eyes also met inclusion criteria and were analyzed as a secondary endpoint. For the 30 study eyes, mean square root of GA area measurements ± standard deviation at baseline were 2.55 ± 0.94 and 2.02 ± 0.74 mm in the eculizumab and placebo groups, respectively (P = 0.13). At 26 weeks, GA enlarged by a mean of 0.19 ± 0.12 and 0.18 ± 0.15 mm in the eculizumab and placebo groups, respectively (P = 0.96). At 52 weeks of follow-up, GA enlarged by a mean of 0.37 ± 0.22 mm in the eculizumab-treated eyes and by a mean of 0.37 ± 0.21 mm in the placebo group (P = 0.93, 2 sample t test). None of the eyes converted to wet AMD. No drug-related adverse events were identified. CONCLUSIONS: Systemic complement inhibition with eculizumab was well tolerated through 6 months but did not decrease the growth rate of GA significantly. However, there was a statistically significant correlation between the low-luminance deficit at baseline and the progression of GA over 6 months.

Comparison of Geographic Atrophy Growth Rates Using Different Imaging Modalities in the COMPLETE Study.

BACKGROUND AND OBJECTIVE: To compare the measurements and growth rates of geographic atrophy (GA) secondary to age-related macular degeneration (AMD) obtained using different imaging modalities. PATIENTS AND METHODS: Thirty patients with AMD and GA measuring from 1.25 mm² to 18 mm² based on spectral-domain optical coherence tomography (SD-OCT) fundus imaging were enrolled. Imaging was performed at baseline and at follow-up months 3, 6, 9, and 12, including autofluorescence (AF) imaging with a fundus camera-based flash system (TRC-50DX; Topcon Medical Systems, Oakland, NJ; AF excitation λ: 535-585 nm; detection λ: 605-715 nm), AF and fluorescein angiography (FA) imaging with a confocal scanning laser ophthalmoscopy (SLO) system (Spectralis; Heidelberg Engineering, Heidelberg, Germany; AF excitation λ: 488 nm; detection λ: > 500 nm), and SD-OCT en face imaging (Cirrus; Carl Zeiss Meditec, Dublin, CA). RESULTS: Average baseline square root measurements and enlargement rates of square root areas appeared similar across all modalities; 0.2 mm was the largest difference between any pair of measurement means. The intraclass correlation coefficients (ICC) were essentially equal to 1 for all comparisons of area measurements but were lower for growth rates than area measurements. Comparison of 26-week average enlargement rates showed no significant difference between the SLO AF image and enhanced SD-OCT en face image (mean difference: 0.01 mm; SD: 0.10; P = .70). CONCLUSION: Agreement among all imaging modalities in measuring the areas of GA at baseline diminished when the growth rates of GA were compared over 26 weeks, likely because each imaging technique identifies different anatomic features along the border of GA, which may appear similar but change at different rates.

Association Between Growth of Geographic Atrophy and the Complement Factor I Locus.

The association between the growth of geographic atrophy (GA) and a single nucleotide polymorphism (SNP) in the complement factor I (CFI) locus was investigated in the COMPLETE trial. Growth of GA at 52 weeks in eyes without the CFI at-risk allele was slightly faster than the growth in eyes with the CFI at-risk allele (P ≥ .72). The authors of the current study found that in contrast to the faster growth rate reported in CFI-positive eyes from the MAHALO trial, the CFI positive eyes in the COMPLETE trial did not grow faster, and this analysis included 24 eyes that met the MAHALO eligibility criteria.

Association Between Subfoveal Choroidal Thickness, Reticular Pseudodrusen, and Geographic Atrophy in Age-Related Macular Degeneration.

BACKGROUND AND OBJECTIVE: To compare subfoveal choroidal thickness (CT) measurements in eyes with nonexudative age-related macular degeneration (AMD) in the presence or absence of reticular pseudodrusen (RPD). PATIENTS AND METHODS: Subfoveal CT measurements obtained from patients with AMD enrolled in the COMPLETE study (30 drusen-only eyes and 30 eyes with geographic atrophy [GA]) were compared with an age-distributed normal control group. Multimodal images were evaluated to detect the presence of RPD. RESULTS: After controlling for age and axial length, the mean CT was significantly thinner in the GA group with RPD (213.7 ± 53.1 µm) than in the GA group without RPD (335.3 ± 123.2 µm; P = .001). The mean CT in the GA group without RPD was not statistically different from the mean CT in the normal control group (P = .076) or the drusen group without RPD (P = .45). In eyes without RPD, there was a correlation between the increasing size of GA and a decrease in CT measurements. CONCLUSION: Subfoveal choroidal thinning in eyes with nonexudative AMD was associated with the presence of RPD. In the absence of RPD, CT only decreased as the size of GA increased.

Spectral-domain optical coherence tomography measurements of choroidal thickness and outer retinal disruption in macular telangiectasia type 2.

BACKGROUND AND OBJECTIVE: To evaluate subfoveal choroidal thickness (CT) and the extent of outer retinal disruption in patients with macular telangiectasia type 2 (MacTel2) compared with healthy eyes. PATIENTS AND METHODS: In this prospective, observational, cohort study, 62 patients (62 eyes) with Mac-Tel2 and 130 healthy controls (130 eyes) underwent a complete ophthalmological examination, spectral-domain optical coherence tomography (SD-OCT) imaging, and axial length measurements. Patients in the study group also underwent color fundus photography, fundus autofluorescence, and fluorescein angiography. En face SD-OCT imaging was used to assess abnormalities involving the photoreceptor inner segment/outer segment/ellipsoid zone (IS/OS/EZ). RESULTS: After adjusting for age and axial length, the authors found that eyes with MacTel2 had a mean CT measurement that was greater than control eyes (P = .007). There was a negative correlation between the visual acuity and the area of IS/OS/EZ damage (P = .009), but no statistically significant correlation was seen between CT and the area of IS/OS/EZ damage. CONCLUSION: Eyes with MacTel2 were found to have thicker CT measurements than control eyes. While the extent of IS/OS/EZ disruption correlated with the loss of visual acuity, this damage did not correlate with CT measurements.

Socioeconomic conditions as determining factors in the prevalence of systemic and ocular toxoplasmosis in Northeastern Brazil.

OBJECTIVE: To determine the prevalence of systemic and ocular toxoplasmosis among 1024 students in the city of Natal, Northeastern Brazil, and correlate it with demographic, socioeconomic and epidemiological risk factors. METHODS: The study population was randomly selected, asked to fill out a questionnaire, provide a blood sample for IgG and IgM (MEIA) serology and a hemogram, and undergo an eye examination. RESULTS: The seroprevalence for IgG was 46% (95% CI = 42.9-49.2%) and that for IgM was 1.4% (95% CI = 0.8-2.4%). The prevalence of ocular lesions was 1.15% (95% CI = 0.6-2.0%). In the univariate analyses, confirmed by multivariate analysis, the socioeconomic conditions were determinants in the prevalence of systemic and ocular toxoplasmosis (mother's schooling = literacy/OR = 2.9 and p < 0.001). CONCLUSIONS: The prevalence of systemic toxoplasmosis, although high, was lower than that found in studies performed in the South and Southeast of Brazil, and the incidence of ocular lesions was totally different, being lower by a factor varying from 5 to 17. Although important epidemiological variables, such as owning a cat, drinking unfiltered water or having had contact with lakes or rivers, were found to be correlated with toxoplasmosis in the preliminary analysis, they lost their influence when included in the logistic model. However, further studies must be undertaken to identify the reasons for these findings, including the determination of the strains of Toxoplasma gondii encountered in different regions of the country and the sources of the water utilized by these populations.

Increasing volume of a retinal pigmented epithelial detachment as a predictor of submacular hemorrhage during anti-VEGF therapy.

Vascularized retinal pigment epithelium detachments (PEDs) are part of the spectrum of neovascular age-related macular degeneration (AMD). These patients with vascularized PEDs are at a higher risk of experiencing severe vision loss. This case report demonstrates the use of a new spectral-domain optical coherence tomography (SD-OCT) algorithm to measure the area and volume of PEDs. When this algorithm was applied to the scans from a patient with a vascularized PED who developed a large submacular hemorrhage while undergoing ranibizumab therapy, the authors found that the algorithm measured an increase in the area and volume of the PED that preceded the macular hemorrhage. Although further studies are needed, the increase in the volume of a PED may serve as a useful predictor of disease progression and the need for more aggressive anti-VEGF therapy.

Diffuse unilateral subacute neuroretinitis.

Diffuse unilateral subacute neuroretinitis (DUSN) is a usually unilateral inflammatory disease characterized by an insidious, usually severe loss of peripheral and central vision. Clinical characteristics are manifested in early and late stages. Parasites of different sizes and several species of nematodes have been reported as the etiology of DUSN without conclusive evidence about the specific agent. Because serologic testing has been variable, the definitive diagnosis is made when the clinical characteristics of DUSN are found in conjunction with an intraocular worm. Laser photocoagulation, pars plana vitrectomy, thiabendazole, and albendazole have been used to treat DUSN with variable success.

Clinical features of 121 patients with diffuse unilateral subacute neuroretinitis.

PURPOSE: To describe the determinant clinical signs to diagnose diffuse unilateral subacute neuroretinitis (DUSN) and the main features related to identification of the live worm. DESIGN: Retrospective study performed at the Federal University of Rio Grande do Norte, Rio Grande do Norte, Brazil, between 2003 and 2008. METHODS: Patients with early- or late-stage diffuse unilateral subacute neuroretinitis were included. All patients underwent complete ophthalmologic examination and had a minimum of 6 months of follow-up. RESULTS: A total of 121 patients were included. Most patients were younger than 20 years (69.42%). Visual acuity was 20/400 or worse in 86 patients (71.7%). Nine patients (7.43%) presented in the early stage and 112 (92.57%) patients presented in the late stage. Subretinal tracks (91.7%), focal alterations of the retinal pigment epithelium (89.3%), small white spots (80.2%), and optic nerve atrophy (76.9%) were the most frequent clinical features. The subretinal worm was identified in 48 patients (39.66%), and laser treatment to destroy it was performed in all cases. The most common location of the nematode was the posterior pole (21 patients). It was observed that the younger the age, the higher the indices of larvae identification (P=.022). Multifocal yellow-white lesions and vitritis were correlated with identification of the worm (P=.001). Mean logarithm of the minimal angle of resolution visual acuity was 1.466 (20/600) and 1.281 (20/400) before and after laser treatment, respectively (P<.005). CONCLUSIONS: Identification of clinical signs and diagnosis of diffuse unilateral subacute neuroretinitis in its early stage, followed by prompt location and destruction of the worm by photocoagulation, may improve the vision of affected patients.