Faricimab in Previously Treated Eyes With Neovascular Age-Related Macular Degeneration: An Assessment of Durability and Treatment Outcomes.

BACKGROUND AND OBJECTIVE: This study evaluated the efficacy and durability of faricimab in patients with neovascular age-related macular degeneration (nAMD) who were previously treated with anti-vascular endothelial growth factor (anti-VEGF) agents. PATIENTS AND METHODS: This retrospective case series was conducted at a single tertiary center in the United States. It focused on nAMD patients who transitioned to faricimab after initial anti-VEGF therapy, with a follow-up period of at least 9 months. "Complete dryness" was defined as the absence of intra- and/or subretinal fluid on optical coherence tomography. Durability was gauged by the extension of treatment intervals relative to the injection frequency of the previous agent. RESULTS: Sixty-two eyes from 62 patients were included. Treatment interval ranged from 5 to 10 weeks; 10 (16%) patients were able to be extended by 2 or more weeks compared to their previous regimen. Median (interquartile range [IQR]) central field thickness was 310 µm (254, 376) on initiating faricimab and declined by the ninth month (P values at 3, 6, and 9 months were 0.01, 0.02, and 0.07, respectively). Median (IQR) visual acuity at initiation of faricimab was 0.4 (0.20, 0.50) and did not change by the ninth month. Complete anatomical dryness was present in 10 (16%) eyes before switching; 90% remained dry at 9 months. Of 52 (84%) incompletely dry eyes before switching, 15% achieved complete dryness by 9 months on faricimab. CONCLUSIONS: Faricimab modestly improved the treatment intervals for a small proportion of previously treated patients on anti-VEGF therapy. [Ophthalmic Surg Lasers Imaging Retina 2024;55:XX-XX.].

Replacement of polyps with type 1 macular neovascularization in polypoidal choroidal vasculopathy imaged with swept source OCT angiography.

PURPOSE: To investigate the morphological changes of polyps in eyes with polypoidal choroidal vasculopathy (PCV) after treatment with vascular endothelial growth factor (VEGF) inhibitors using swept source optical coherence tomography angiography (SS-OCTA). OBSERVATIONS: Following anti-VEGF therapy, polyps were found to evolve into typical type 1 macular neovascularization (MNV) in five eyes. In all of these five eyes, a polypoidal lesion was detected adjacent to a serous or hemorrhagic retinal pigment epithelial detachment (PED). CONCLUSIONS AND IMPORTANCE: Polypoidal lesions in PCV can evolve into typical type 1 MNV. This morphological evolution suggests that these polyps are clusters of tangled vessels that can proliferate into a more typical neovascular pattern, and this evolution may be facilitated by being adjacent to a PED. Since this morphological appearance could be associated with a better prognosis, SS-OCTA might be helpful in identifying cases of transformed polyps that may be associated with a decreased risk for vision loss.

The Extent of Retinal Involvement of Canthaxanthin Crystalline Retinopathy Demonstrated by Multimodal Imaging.

Limited information is known about the extent of canthaxanthin crystalline retinopathy on the retinal layers. The authors describe a 51-year-old woman who was taking canthaxanthin for tanning purposes for 7 years. Three years after cessation of this agent, she presented with asymmetric crystalline retinopathy affecting both eyes. She was lost to follow-up, and upon returning 4 years later, the crystalline retinopathy persisted but the number of crystals had decreased. Using swept-source optical coherence tomography, the authors showed that the crystalline retinopathy affected all retinal layers. In addition, retinal pigmented epithelial detachments were present suggesting persistent damage caused by the canthaxanthin. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:727-731.].

New method of sudomotor function measurement to detect microvascular disease and sweat gland nerve or unmyelinated C fiber dysfunction in adults with retinopathy.

BACKGROUND: Diabetes-associated microvascular complications such as retinopathy and neuropathy often lead to end-organ and tissue damage. Impaired skin microcirculation often precedes the detection of other advanced diabetic complications. The ANS-1 system contains a redesigned sympathetic skin response (ANS-1 SSR) device that measures sudomotor function, a photoplethysmography sensor, and a blood pressure device to comprehensively assess cardiac autonomic neuropathy and endothelial dysfunction. The purpose of this study was to determine the relationships between the ANS-1 SSR amplitude measured at the: (a) negative electrode (Nitric Oxide [NO] Sweat Peak) with microvascular diseases and associated vascular blood markers and (b) positive electrode (iSweat Peak) with C fiber function. METHODS: All participants (healthy controls n = 50 and retinopathy patients n = 50) completed the ANS-1 system evaluation and a basic sociodemographic and medical history questionnaire, including a quality of life measure (SF-36). A small sample of blood was drawn to determine levels of homocysteine, blood urea nitrogen (BUN), C-reactive protein (CRP), and fibrinogen. Symptoms of peripheral foot neuropathy were assessed with a scale from 1 (none) to 10 (the worst). We used Spearman rank correlations, independent samples t-tests, and receiver operating characteristic curves to determine the specificity and sensitivity of the NO Sweat Peak as a potential screening marker of retinopathy. RESULTS: The ANS-1 System Cardiometabolic Risk Score and all indicators of quality of life on the SF-36, other than Emotional Role Functioning, were significantly worse in the retinopathy patients. The sudomotor response marker NO Sweat Peak had a sensitivity of 88% and a specificity of 68% (Area Under the Curve = 0.81, p < 0.0001) to detect retinopathy. The NO Sweat Peak response marker inversely correlated with BUN (ρ = -0.41, p < 0.0001), homocysteine (ρ = -0.44, p < 0.0001), fibrinogen (ρ = -0.41, p < 0.0001), the Cardiac Autonomic Neuropathy score (ρ = -0.68, p < 0.0001), and the heart rate variability Total Power (ρ = -0.57, p < 0.0001), and it positively correlated with the Photoplethysmography Index (PTGi; ρ = 0.53 p < 0.0001). The ANS-1 system sudomotor response marker iSweat Peak inversely correlated with the severity of symptoms on the peripheral neuropathy scale (ρ = -0.56, p < 0.0001). CONCLUSION: The results of the study show that this new method of measuring sympathetic skin response should be useful for detecting the earliest manifestations of microvascular disease and symptoms of C fiber dysfunction.

Comparison Between Spectral-Domain and Swept-Source Optical Coherence Tomography Angiographic Imaging of Choroidal Neovascularization.

Purpose: The purpose of this study was to compare imaging of choroidal neovascularization (CNV) using swept-source (SS) and spectral-domain (SD) optical coherence tomography angiography (OCTA). Methods: Optical coherence tomography angiography was performed using a 100-kHz SS-OCT instrument and a 68-kHz SD-OCTA instrument (Carl Zeiss Meditec, Inc.). Both 3 × 3- and 6 × 6-mm2 scans were obtained on both instruments. The 3 × 3-mm2 SS-OCTA scans consisted of 300 A-scans per B-scan at 300 B-scan positions, and the SD-OCTA scans consisted of 245 A-scans at 245 B-scan positions. The 6 × 6-mm2 SS-OCTA scans consisted of 420 A-scans per B-scan at 420 B-scan positions, and the SD-OCTA scans consisted of 350 A-scans and 350 B-scan positions. B-scans were repeated four times at each position in the 3 × 3-mm2 scans and twice in the 6 × 6-mm2 scans. Choroidal neovascularization was excluded if not fully contained within the 3 × 3-mm2 scans. The same algorithm was used to detect CNV on both instruments. Two graders outlined the CNV, and the lesion areas were compared between instruments. Results: Twenty-seven consecutive eyes from 23 patients were analyzed. For the 3 × 3-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.17 and 1.01 mm2, respectively (P = 0.047). For the 6 × 6-mm2 scans, the mean lesion areas for the SS-OCTA and SD-OCTA instruments were 1.24 and 0.74 mm2 (P = 0.003). Conclusions: The areas of CNV tended to be larger when imaged with SS-OCTA than with SD-OCTA, and this difference was greater for the 6 × 6-mm2 scans.

Automated Quantitation of Choroidal Neovascularization: A Comparison Study Between Spectral-Domain and Swept-Source OCT Angiograms.

Purpose: To compare the lesion sizes of choroidal neovascularization (CNV) imaged with spectral-domain (SD) and swept-source (SS) optical coherence tomography angiography (OCTA) and measured using an automated detection algorithm. Methods: Patients diagnosed with CNV were imaged by SD-OCTA and SS-OCTA systems using 3 × 3-mm and 6 × 6-mm scans. The complex optical microangiography (OMAGC) algorithm was used to generate the OCTA images. Optical coherence tomography A datasets for imaging CNV were derived by segmenting from the outer retina to 8 µm below Bruch's membrane. An artifact removal algorithm was used to generate angiograms free of retinal vessel projection artifacts. An automated detection algorithm was developed to quantify the size of the CNV. Automated measurements were compared with manual measurements. Measurements from SD-OCTA and SS-OCTA instruments were compared as well. Results: Twenty-seven eyes from 23 subjects diagnosed with CNV were analyzed. No significant differences were detected between manual and automatic measurements: SD-OCTA 3 × 3-mm (P = 0.61, paired t-test) and 6 × 6-mm (P = 0.09, paired t-test) scans and the SS-OCTA 3 × 3-mm (P = 0.41, paired t-test) and 6 × 6-mm (P = 0.16, paired t-test) scans. Bland-Altman analyses were performed to confirm the agreement between automatic and manual measurements. Mean lesion sizes were significantly larger for the SS-OCTA images compared with the SD-OCTA images: 3 × 3-mm scans (P = 0.011, paired sample t-test) and the 6 × 6-mm scans (P = 0.021, paired t-test). Conclusions: The automated algorithm measurements of CNV were in agreement with the hand-drawn measurements. On average, automated SS-OCTA measurements were larger than SD-OCTA measurements and consistent with the results from using hand-drawn measurements.

Anatomic Clinical Trial Endpoints for Nonexudative Age-Related Macular Degeneration.

TOPIC: To review the role of anatomic endpoints in clinical trials for the study of nonexudative age-related macular degeneration (AMD) with an emphasis on a novel composite endpoint for the study of emerging therapies for intermediate AMD (iAMD). CLINICAL RELEVANCE: Unlike clinical trials for exudative AMD, it is impractical to use the change in visual acuity (VA) as a primary endpoint for the study of nonexudative AMD. By the time VA has been lost in nonexudative AMD, proof-of-concept early-stage clinical trials would take years to run, and drug development would be a near impossible task. Surrogate endpoints are needed that reliably predict future vision loss and can be easily measured. Anatomic changes that correlate with disease progression in nonexudative AMD offer the greatest promise as primary endpoints. METHODS: In preparation for this review, the electronic PubMed database was searched for relevant research pertaining to anatomic endpoints for the study of nonexudative AMD. Paper selection was based on our knowledge of the field with the goal to be as inclusive as possible. Whenever possible, recent review articles and results from large clinical trials, preferably with outcomes from many years of follow-up were favored over trials of short duration. RESULTS: The most commonly used anatomic endpoint for the study of late, nonexudative AMD is the growth of geographic atrophy (GA). The advantages of studying GA include the appreciation that its enlargement through the foveal center leads to significant vision loss through the availability of natural history studies, the understanding that prevention of this growth would preserve vision in the future, the ability to reliably measure GA using different imaging strategies, and the development appropriate statistical tools that reliably predict the growth of GA over time. The major disadvantage of using GA is that significant, irreversible disease progression has already occurred. The use of drusen volume as a predictor of disease progression and the use of a composite endpoint that incorporates drusen growth, formation of GA, and formation of neovascularization offers an opportunity to study therapies at an earlier stage of AMD with a greater likelihood of preserving better vision over a lifetime. CONCLUSIONS: Anatomic endpoints for the study of nonexudative AMD are needed to accelerate drug development, and the availability of optical coherence tomography algorithms capable of reliably measuring drusen morphology offer the best opportunity to study therapies for iAMD.

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.

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.

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.

Optical coherence tomography measurements of choroidal thickness in healthy eyes: correlation with age and axial length.

BACKGROUND AND OBJECTIVE: To evaluate subfoveal choroidal thickness (CT) in healthy eyes using spectral-domain optical coherence tomography (SD-OCT) and provide correlations between age and axial length. PATIENTS AND METHODS: Enhanced depth SD-OCT imaging was performed with Cirrus (Carl Zeiss Meditec, Dublin, CA) and Spectralis (Heidelberg Engineering, Heidelberg, Germany) instruments. CT was measured from the outer limit of the retinal pigment epithelium to the inner surface of the sclera. RESULTS: The study enrolled 155 patients, with at least 20 in each decade between 22 and 89 years old. Mean axial length was 23.6 mm. Mean Heidelberg subfoveal CT was 286 µm. The correlation between Heidelberg and Zeiss subfoveal CT measurements was strong (r = .978) and significant (P < .001). Mean subfoveal CT was 7.7 µm thinner by Heidelberg versus Cirrus (P < .001). Multiple linear regression analysis revealed that age (P < .001), axial length (P = .001), and sex (P = .025) were significantly related to Heidelberg subfoveal CT. CONCLUSION: There is a strong negative correlation between CT and age (P <.001), with a 25 µm decrease in CT for each decade of life. Increasing axial length demonstrated a negative correlation with CT, decreasing 24.9 µm for each mm of axial length. Future studies of CT measurements can be performed on either instrument and must account for axial length, age, and sex to make appropriate conclusions.

Purtscher-Like Retinopathy and Diffuse Alveolar Hemorrhage Caused by Soft Tissue Injection for Gluteal Augmentation.

PURPOSE: To describe a rare occurrence of acute vision loss and diffuse alveolar hemorrhage following a treatment of injectable gluteal cosmetic filler. PATIENT AND METHODS: A 20-year-old female underwent a cosmetic injection of unknown components for gluteal augmentation. Within hours she developed progressive shortness of breath secondary to diffuse alveolar hemorrhage. She presented to ophthalmology 6 weeks later with a history of bilateral decreased vision. Clinical examination revealed cotton wool spots and retinal hemorrhages. Fluorescein angiography demonstrated macular vascular pruning and an enlarged foveal avascular zone. RESULTS: The patient was observed and vision did not improve after 8 months of follow-up. CONCLUSION: These findings were attributed to a Purtscher-like retinopathy secondary to systemic inflammation induced by the filler and/or direct microembolization of the injected material or fat. To the best of the authors' knowledge, this is the first documented case of diffuse alveolar hemorrhage and ischemic bilateral vision loss in a patient undergoing gluteal augmentation with dermal filler.

Response to aflibercept after frequent re-treatment with bevacizumab or ranibizumab in eyes with neovascular AMD.

BACKGROUND AND OBJECTIVE: To evaluate the effects of switching to aflibercept in eyes with neovascular age-related macular degeneration (AMD) requiring frequent re-treatment with bevacizumab or ranibizumab. PATIENTS AND METHODS: Retrospective review of 73 eyes of 65 patients with neovascular AMD switched to aflibercept due to persistent or recurrent macular fluid after at least 1 year of intravitreal bevacizumab or ranibizumab with re-treatment at least every 6 weeks. Minimum post-switch follow-up was 6 months. All patients were treated using a treat-and-extend strategy. The treatment intervals immediately after and before the switch were the same. RESULTS: The mean pre-switch anti-VEGF therapy duration was 45 months, and the mean number of injections was 31. In the 6 months after the switch, the average number of injections was reduced by 0.6 compared with the 6 months before the switch (P < .001). Visual acuity was unchanged during this period (P = .78). Central retinal thickness (CRT) decreased by 19 µm after the switch (P < .001). Seventy eyes had vascularized retinal pigment epithelial detachments (PEDs). The decrease in the PED cube-root volume during the 6 months after the switch was statistically significant (-0.07 mm; P = .007). CONCLUSION: The number of injections, CRT, and PED volume decreased significantly after the switch to aflibercept, but visual acuity was unchanged.

Change in drusen area over time compared using spectral-domain optical coherence tomography and color fundus imaging.

PURPOSE: To investigate the relationship between drusen areas measured with color fundus images (CFIs) and those with spectral-domain optical coherence tomography (SDOCT). METHODS: Forty-two eyes from thirty patients with drusen in the absence of geographic atrophy were recruited to a prospective study. Digital color fundus images and SDOCT images were obtained at baseline and at follow-up visits at 3 and 6 months. Registered, matched circles centered on the fovea with diameters of 3 mm and 5 mm were identified on both CFIs and SDOCT images. Spectral-domain OCT drusen measurements were obtained using a commercially available proprietary algorithm. Drusen boundaries on CFIs were traced manually at the Doheny Eye Institute Image Reading Center. RESULTS: Mean square root drusen area (SQDA) measurements for the 3-mm circles on the SDOCT images were 1.451 mm at baseline and 1.464 mm at week 26, whereas the measurements on CFIs were 1.555 mm at baseline and 1.584 mm at week 26. Mean SQDA measurements from CFIs were larger than those from the SDOCT measurements at all time points (P = 0.004 at baseline, P = 0.003 at 26 weeks). Changes in SQDA over 26 weeks measured with SDOCT were not different from those measured with CFIs (mean difference = 0.014 mm, P = 0.5). CONCLUSIONS: Spectral-domain OCT drusen area measurements were smaller than the measurements obtained from CFIs. However, there were no differences in the change in drusen area over time between the two imaging modalities. Spectral-domain OCT measurements were considerably more sensitive in assessing drusen area changes.

Bilateral papillopathy as a presenting sign of pheochromocytoma associated with von Hippel-Lindau disease.

A 7-year-old girl presented with decreased vision in both eyes for 1 month. Examination showed visual acuity of 20/50 and 20/60, no afferent pupillary defect, cecocentral scotomas, and bilateral optic disc edema with extensive peripapillary and macular exudates. Magnetic resonance imaging showed multiple cortical and subcortical white matter lesions. Both the laboratory workup and the systemic examination were unrevealing. However, on follow-up, the patient showed episodic elevations of blood pressure as high as 240/160. Further workup revealed elevated urine catecholamines and a right supra-adrenal mass proven to be a pheochromocytoma by histopathologic analysis. The paroxysmal hypertension resolved, and the visual acuity, visual fields, fundus exam, and neuroimaging improved. The patient was lost to follow-up until age 18 when she developed shortness of breath and was found to have multiple pulmonary metastases identified as pheochromocytoma by biopsy. Genetic testing identified a 3p25-26 (c.482 G>A) VHL gene chromosomal mutation consistent with von Hippel-Lindau disease genotype. Multiple peripheral retinal vascular dilations and small retinal capillary hemangioblastomas were also found. This case highlights the importance of recognizing the lability of blood pressure often seen with pheochromocytomas, which may mask the underlying cause of hypertensive papillopathy and retinopathy, a diagnosis of low clinical suspicion in the pediatric population. The case also underscores the importance of thorough systemic workup, including genotyping to detect conditions where pheochromocytoma may be the presenting sign of the disease, such as multiple endocrine neoplasia 2A and 2B, von Hippel-Lindau disease, von Recklinghausen disease, tuberous sclerosis, and Sturge-Weber syndrome.

OCT minimum intensity as a predictor of geographic atrophy enlargement.

PURPOSE: We determined whether the minimum intensity (MI) of the optical coherence tomography (OCT) A-scans within the retina can predict locations of growth at the margin of geographic atrophy (GA) and the growth rate outside the margin. METHODS: The OCT scans were analyzed at baseline and 52 weeks. Expert graders manually segmented OCT images of GA. The 52-week follow-up scans were registered to the baseline scan coordinates for comparison. The OCT MI values were studied within a 180-µm margin around the boundary of GA at baseline. Baseline MI values were compared in areas of progression and nonprogression of the GA, and sensitivity and specificity were assessed for prediction of growth at the margin. Average MI values in the margins were compared to overall growth rates to evaluate the prediction of growth outside the margins. RESULTS: A statistically significant increase in MI (P < 0.05) was seen in areas of growth in 21/24 cases (88%), and 22/24 cases (92%) when the foveal subfield was excluded. Locations of growth within the margins at 52 weeks were predicted with 61% sensitivity and 61% specificity. The MI values correlated significantly with overall growth rate, and high and low growth rate subjects were identified with 80% sensitivity and 64% specificity. CONCLUSIONS: The MI may be increased at the margins of GA lesions before enlargement, which may indicate disruption or atrophy of the photoreceptors in these areas before GA becomes apparent. Increased MI may help predict areas of enlargement of GA, and may relate to overall growth rate and be a useful screening tool for GA. (ClinicalTrials.gov number, NCT00935883.).

Change in drusen volume as a novel clinical trial endpoint for the study of complement inhibition in age-related macular degeneration.

BACKGROUND AND OBJECTIVE: To evaluate the change in drusen volume following treatment with eculizumab, a systemic inhibitor of complement component 5. PATIENTS AND METHODS: Single-center, prospective, randomized, double-masked clinical trial. Patients were randomized 2:1 to receive intravenous eculizumab or placebo over 26 weeks. MAIN OUTCOME MEASURE: decrease in drusen volume of at least 50% at 26-week follow-up. RESULTS: Mean drusen cube root volumes were 0.49 mm and 0.47 mm (P = .64) at baseline and 0.51 mm and 0.42 mm (P = .17) at 26 weeks in the eculizumab and placebo groups, respectively. In the placebo group, one eye had a decrease in drusen volume of at least 50% and two eyes developed neovascularization through 26 weeks. CONCLUSION: Systemic complement inhibition with eculizumab did not significantly reduce drusen volume. Drusen growth was dependent on the number of complement at-risk alleles. Future trials should consider the use of a composite clinical trial endpoint in which efficacy is defined by the treatment's ability to prevent drusen growth, neovascularization, and the formation of geographic atrophy over 1 year.

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.

Predicting the progression of geographic atrophy in age-related macular degeneration with SD-OCT en face imaging of the outer retina.

BACKGROUND AND OBJECTIVE: Spectral-domain optical coherence tomography (SD-OCT) en face imaging was used to measure the growth of geographic atrophy (GA) and identify baseline anatomic changes in the outer retina in eyes with nonexudative age-related macular degeneration (AMD). PATIENTS AND METHODS: In this prospective study, eyes were imaged using 200 × 200 and 512 × 128 A-scan raster patterns. Outer retinal anatomy was visualized using en face imaging of a 20-µm thick slab encompassing the inner segment/outer segment (IS/OS) band. RESULTS: En face SD-OCT imaging of the IS/OS region revealed a bilaterally symmetrical pattern of outer retinal disruption extending beyond the borders of GA that accurately predicted the progression of GA over 1 year in 13 of 30 eyes (43.3%). In the remaining cases, the area of disruption was much larger than the area of progression. CONCLUSION: En face imaging of the outer retina can predict the growth of GA in some eyes. Due to the bilateral symmetry of these findings, this imaging strategy may identify a genetic subset of patients in whom photoreceptor loss precedes the progression of GA. These areas with outer retinal disruption should be followed in clinical trials designed to test treatments for dry AMD.