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.

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.

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.].

Quantitative changes in retinal pigment epithelial detachments as a predictor for retreatment with anti-VEGF therapy.

PURPOSE: To determine if quantitative changes in retinal pigment epithelial detachments (PEDs) predict the need for retreatment in eyes undergoing spectral domain optical coherence tomography (SD OCT)-guided as-needed therapy with anti-vascular endothelial growth factor drugs. METHODS: Patients with vascularized PEDs undergoing SD OCT-guided treatment with anti-vascular endothelial growth factor drugs were retrospectively identified. The decision to retreat these cases was based on qualitative assessments of fluid in the macula. Spectral domain OCT images from visits in which the treatment was withheld were retrospectively analyzed. A novel algorithm was then used to measure the area and volume of PEDs at these visits. RESULTS: Fourteen eyes were identified, and retreatment was withheld at 57 visits. When the SD OCT algorithm was used to evaluate the scans from these visits, the PED volume increased at eight visits. At all of these eight visits, a treatment was needed at the next follow-up visit. For the remaining 49 visits in which the treatment was withheld, the PED volume did not increase and no treatment was needed at the next follow-up visit. CONCLUSION: Quantitation of the change in the PED volume and area may be useful in determining when to retreat eyes undergoing SD OCT-guided as-needed anti-vascular endothelial growth factor therapy.

Spectral-domain optical coherence tomography imaging of drusenoid pigment epithelial detachments.

PURPOSE: To evaluate drusenoid retinal pigment epithelial detachments (DPED) secondary to age-related macular degeneration (AMD) using spectral-domain optical coherence tomography imaging. METHODS: In this prospective natural history study, eyes from patients with the diagnosis of nonexudative AMD and DPEDs were followed for at least 6 months. Eyes were scanned using the Cirrus spectral-domain optical coherence tomography instrument and the 200 × 200 A-scan raster pattern. A custom software was used to quantify volumetric changes in DPEDs and to detect the evolution and formation of geographic atrophy and choroidal neovascularization. Changes in DPED area and volume and development of the advanced forms of AMD were the main outcome. RESULTS: Of the 130 patients (186 eyes) with nonadvanced AMD, 11 patients (16 eyes) presented with DPEDs during the study. Mean follow-up was 18.5 months. Most DPEDs had an area exceeding 1 disk area (14 of 16 eyes) based on color fundus images with a mean area of 4.19 mm(2) (SD = 1.35) measured by spectral-domain optical coherence tomography. The mean volume at the time the DPED was diagnosed was 0.48 mm(3) (SD = 0.28). Four different patterns of progression were observed: DPEDs remained unchanged in 8 of 16 eyes (50%), DPEDs tended to increase in volume before progressing to geographic atrophy in 5 eyes (31.25%) and choroidal neovascularization in 2 eyes (12.5%), and a DPED decreased by more than 50% without progressing to geographic atrophy or choroidal neovascularization in 1 eye (6.25%). CONCLUSION: Spectral-domain optical coherence tomography imaging is able to detect subtle changes in the area and volume of DPEDs. Quantitative spectral-domain optical coherence tomography imaging of DPEDs is useful for identifying the natural history of disease progression and as a clinical tool for monitoring eyes with AMD in clinical trials.

Pharmacokinetic rationale for dosing every 2 weeks versus 4 weeks with intravitreal ranibizumab, bevacizumab, and aflibercept (vascular endothelial growth factor Trap-eye).

PURPOSE: Monthly dosing with inhibitors of vascular endothelial growth factor (VEGF) results in stable or improved visual acuity in most patients with neovascular age-related macular degeneration. However, a minority of patients show little if any response to therapy with persistent or worsening macular fluid. Pharmacokinetic modeling was performed to determine if more frequent dosing with anti-VEGF drugs could be theoretically beneficial. METHODS: A mathematical model comparing the time-dependent relative binding activities of ranibizumab, bevacizumab, and aflibercept (VEGF Trap-eye; VTE) was used to determine the theoretical peak and trough binding activities when the drugs were injected every 14 days and every 28 days. The intravitreal half-lives of ranibizumab, bevacizumab, and the VTE were estimated to be 3.2, 5.6, and 4.8 days, respectively. The relative molar binding activities of ranibizumab, bevacizumab, and the VTE used in the analyses were 1, 0.05 to 0.2, and 140, respectively. The expected peak and trough binding activities for ranibizumab, bevacizumab, and VTE were calculated. Dosing every 2 weeks was performed on selected patients who had a poor response to monthly therapy. RESULTS: Dosing of a drug every 2 weeks resulted in markedly improved trough binding activity, but had little impact on the peak binding activity when calculated through Day 28. The dosing of bevacizumab every 2 weeks resulted in trough binding levels that were superior to monthly dosing with ranibizumab at a dose of 0.5 mg and potentially superior to the levels achieved when ranibizumab was dosed monthly at a dose of 2.0 mg. The VTE displayed superior binding levels for both peak and trough levels even when compared with ranibizumab doses given every 2 weeks. Two case reports demonstrate the clinical usefulness of dosing with anti-VEGF therapy every 2 weeks in eyes with VEGF-dependent macular fluid appearing to be refractory to monthly dosing. CONCLUSION: The theoretical increase in trough binding levels when anti-VEGF drugs are dosed every 2 weeks most likely explains the clinical benefit observed in patients who received biweekly injections after their poor response to monthly therapy. The short-term use of biweekly dosing may be an attractive treatment option for those eyes that show a treatment response within 2 weeks of an injection, but rebound with increased macular fluid after a month. In the future, VTE should provide higher trough levels of anti-VEGF binding activity and eliminate the need for biweekly dosing in those eyes with VEGF-mediated exudation that appear unresponsive to monthly ranibizumab or bevacizumab.

Strategies for following dry age-related macular degeneration.

Spectral domain optical coherence tomography (SDOCT) provides a novel strategy for imaging and monitoring progression in patients with age-related macular degeneration (AMD). The advantage of SDOCT over other imaging modalities or functional tests is that one modality can be used to image both drusen and geographic atrophy while obtaining reproducible, quantitative data on both drusen morphology and the area of geographic atrophy. Moreover, this strategy enables the clinician to follow the disease as it progresses from drusen to both geographic atrophy and choroidal neovascularization. No other imaging modality is able to quantitatively assess all forms of AMD. This unique feature of SDOCT makes it the ideal imaging modality for monitoring patients with AMD, providing routine care, and for following patients in clinical trials designed to assess the efficacy of new drugs for the treatment of dry AMD.

Natural history of drusen morphology in age-related macular degeneration using spectral domain optical coherence tomography.

PURPOSE: To characterize the natural history of drusen using spectral-domain optical coherence tomography (SD-OCT) imaging of eyes from patients with nonexudative age-related macular degeneration (AMD). DESIGN: Prospective, longitudinal, natural history study. PARTICIPANTS: We included 143 eyes of 100 patients with at least 6 months of follow-up. METHODS: Patients with drusen secondary to nonexudative AMD were scanned using the Cirrus SD-OCT instrument. Eyes were imaged using the 200 × 200 A-scan raster pattern contained within a 6 × 6 mm area. Custom software was used to quantify volumetric changes in drusen over a period of ≥ 6 months and for as long as 24 months. Drusen volume and drusen area were measured within circular regions centered at the fovea having diameters of 3 and 5 mm. The measurements were analyzed using a suitable scale transformation. For drusen volume, a cube root transformation strategy was used. MAIN OUTCOME MEASURES: Change in drusen volume and area over time. RESULTS: We analyzed 143 eyes of 100 patients with 69 eyes followed for 6 months, 106 eyes followed for 12 months, 48 eyes followed for 18 months, and 48 eyes followed for 24 months. The 3 mm circle baseline drusen volume ranged from 0.0009 to 0.7479 mm(3) or 0.10 to 0.91 mm using the cube root scale. On average, drusen volume and drusen area increased over time with the magnitude of the increase dependent on the length of follow-up (P = 0.001, 3 mm circle). In the eyes with a decrease in drusen volume, the magnitude of this decrease was dependent on the baseline drusen volume (P = 0.001, 3 mm circle) and independent of the follow-up interval. After 12 months, drusen volume increased in 48% of eyes, remained stable in 40%, and decreased in 12%. CONCLUSIONS: Imaging with SD-OCT revealed a dynamic, undulating growth pattern for drusen with a tendency for drusen to increase in volume and area over time. An appreciation of the quantitative changes in drusen volume over time using SD-OCT imaging provides a novel strategy for following normal disease progression and for identifying novel clinical trial end points to be used when investigating therapies for the treatment of nonexudative AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Progression of geographic atrophy in age-related macular degeneration imaged with spectral domain optical coherence tomography.

PURPOSE: To determine the area and enlargement rate (ER) of geographic atrophy (GA) in patients with age-related macular degeneration (AMD) using the spectral domain optical coherence tomography (SD-OCT) fundus image. DESIGN: Prospective, longitudinal, natural history study. PARTICIPANTS: Eighty-six eyes of 64 patients with ≥6 months of follow-up. METHODS: Patients with GA secondary to AMD were enrolled in this study. Macular scans were performed using the Cirrus SD-OCT (Carl Zeiss Meditec, Dublin, CA). The areas of GA identified on the SD-OCT fundus images were quantified using a digitizing tablet. Reproducibility of these measurements was assessed and the ER of GA was calculated. The usefulness of performing square root transformations of the lesion area measurements was explored. MAIN OUTCOME MEASURES: Enlargement rate of GA. RESULTS: At baseline, 27% of eyes had a single area of GA. The mean total area at baseline was 4.59 mm(2) (1.8 disc areas [DA]). The mean follow-up time was 1.24 years. Reproducibility, as assessed with the intraclass correlation coefficient (ICC), was excellent on both the original area scale (ICC = 0.995) and the square root scale (ICC = 0.996). Intergrader differences were not an important source of variability in lesion size measurement (ICC = 0.999, 0.997). On average, the ER of GA per year was 1.2 mm(2) (0.47 DA; range, 0.01-3.62 mm(2)/year). The ER correlated with the initial area of GA (r = 0.45; P<0.001), but there were variable growth rates for any given baseline area. When the square root transformation of the lesion area measurements was used as a measure of lesion size, the ER (0.28 mm/yr) was not correlated with baseline size (r = -0.09; P = 0.40). In this cohort of lesions, no correlation was found between ER and length of follow-up. Square root transformation of the data helped to facilitate sample size estimates for controlled clinical trials involving GA. CONCLUSIONS: The SD-OCT fundus image can be used to visualize and quantify GA. Advantages of this approach include the convenience and assurance of using a single imaging technique that permits simultaneous visualization of GA along with the loss of photoreceptors and the retinal pigment epithelium that should correlate with the loss of visual function.

Spectral domain optical coherence tomography imaging of drusen in nonexudative age-related macular degeneration.

PURPOSE: To measure drusen area and volume in eyes with nonexudative age-related macular degeneration (AMD) using spectral domain optical coherence tomography imaging (SD-OCT). DESIGN: Evaluation of diagnostic technology. PARTICIPANTS: One hundred three eyes from 74 patients with drusen. METHODS: Patients with drusen secondary to nonexudative AMD were enrolled in this study. Five separate SD-OCT scans, each consisting of 40 000 uniformly spaced A-scans organized as 200 A-scans in each B-scan and 200 horizontal B-scans, were performed on each eye. Each scan covered a retinal area of 6×6 mm centered on the fovea. A novel algorithm was used to quantitatively assess drusen area and volume. Measurements from the entire scans, as well as in regions contained within 3- and 5-mm circles centered on the fovea, were analyzed. Test-retest standard deviations of drusen area and volume measurements were calculated for each eye. MAIN OUTCOME MEASURES: Drusen area and volume. RESULTS: The algorithm created drusen maps that permitted both qualitative and quantitative assessment of drusen area and volume. Both the qualitative appearance and the quantitative measurements of drusen area and volume were highly reproducible over the 5 different datasets. The intraclass correlation coefficient was >0.99 for both area and volume measurements on the entire dataset as well as the 3- and 5-mm circles. The correlation between lesion size and the test-retest standard deviations can be eliminated by performing a square root transformation of the area measurements and a cube root transformation of the volume measurements. These transformed data allowed for the inclusion of all drusen sizes in the calculation of an estimated single pooled test-retest standard deviation, which will be useful for longitudinal studies of drusen natural history. CONCLUSIONS: A novel algorithm for the qualitative and quantitative assessment of drusen imaged using SD-OCT was shown to be highly reproducible. The ability to assess drusen volume reliably represents a new quantitative parameter to measure in AMD and may be useful when assessing disease progression, particularly in trials for treatments of nonexudative AMD.

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.

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.

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.

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.

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.