Retina

RECLASSIFICATION OF FUNDUS AUTOFLUORESCENCE PATTERNS SURROUNDING GEOGRAPHIC ATROPHY BASED ON PROGRESSION RATE: A Systematic Review and Meta-Analysis
Shen, Liangbo L.; Liu, Feimei; Nardini, Holly Grossetta; More
RETINA. 39(10):1829-1839, October 2019.

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Purpose:
To reclassify fundus autofluorescence (FAF) patterns around geographic atrophy (GA) based on GA progression rates.

Methods:
MEDLINE, EMBASE, Cochrane Library, Clinicaltrials.gov , and PubMed were searched for studies reporting GA progression rates among different FAF patterns, such as “None,” “Focal,” “Banded,” “Patchy,” “Diffuse Nontrickling,” and “Diffuse Trickling.” The GA radius growth rate among different FAF patterns was compared, and a GA growth function for each group was derived. To account for the patients' different entry times, a horizontal translation factor was introduced to shift each data subset from “time after enrollment” to “duration of GA.”

Results:
Seven studies with 496 eyes were included. Based on GA radius growth rates, the six FAF patterns were clustered into four groups with a high correlation coefficient within each group: Group 1, None, 0.061 mm/year (r 2 = 0.996), Group 2, Focal, 0.105 mm/year (r 2 = 0.987), Group 3, Banded, Patchy, and Diffuse Nontrickling, 0.149 mm/year (r 2 = 0.993), and Group 4, “Diffuse Trickling, 0.245 mm/year (r 2 = 0.997).

Conclusion:
This meta-analysis suggested that the six FAF patterns can be coalesced into four groups based on lesion progression rates. Simplification of the reclassified FAF patterns may shed light on the GA natural history and assist in the design of clinical trials.

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CHOROIDAL NEVUS IMAGING FEATURES IN 3,806 CASES AND RISK FACTORS FOR TRANSFORMATION INTO MELANOMA IN 2,355 CASES: The 2020 Taylor R. Smith and Victor T. Curtin Lecture
Shields, Carol L.; Dalvin, Lauren A.; Ancona-Lezama, David; More
RETINA. 39(10):1840-1851, October 2019.

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Purpose:
To use multimodal imaging for identification of risk factors for choroidal nevus transformation into melanoma.

Methods:
Retrospective chart review of 3806 consecutive choroidal nevi with imaging and 2355 choroidal nevi with additional follow up to identify factors predictive of transformation of choroidal nevus into melanoma.

Results:
The median patient age was 62.5 years and Caucasian race in 3167 (95%). The choroidal nevus demonstrated median basal diameter of 4.0 mm and thickness of 1.4 mm. Imaging included optical coherence tomography (OCT) showing subretinal fluid (SRF) in 312 (9%), ultrasonography (US) with acoustic hollowness in 309 (9%), and hyper-autofluorescence (AF) in 100 (3%). Of those 2355 choroidal nevi with follow up, Kaplan-Meier estimates of nevus transformation into melanoma at 1, 5, and 10 years were 1.2%, 5.8%, and 13.9%, respectively. Multivariate analysis, using multimodal imaging for detection of factors predictive of nevus transformation into melanoma, included thickness >2 mm on US (hazard ratio (HR) 3.80, p < 0.0001), SRF on OCT as cap over nevus (HR 3.00, p < 0.0001) or SRF ≤3 mm from nevus margin (HR 3.56, p = 0.0003), symptomatic vision loss ≤20/50 on Snellen visual acuity (VA) (HR 2.28, p = 0.005), orange pigment (lipofuscin) hyperautofluorescence on AF (HR 3.07, p = 0.0004), acoustic hollowness on US (HR 2.10, p = 0.0020), and tumor diameter >5 mm on photography (HR 1.84, p = 0.0275). These factors can be recalled by the mnemonic “To Find Small Ocular Melanoma Doing IMaging” (TFSOM-DIM) representing Thickness >2 mm (US), Fluid subretinal (OCT), Symptoms vision loss (VA), Orange pigment (AF), Melanoma hollow (US), and DIaMeter >5mm (photography). The mean 5-year estimates of nevus growth into melanoma were 1% (HR 0.8) for those with 0 risk factor, 11% (HR 3.09) with 1 factor, 22% (HR 10.6) with 2 factors, 34% (HR 15.1) with 3 factors, 51% (HR 15.2) with 4 factors, 55% (HR 26.4) with 5 risk factors, and not-estimable with all 6 risk factors.

Conclusion:
In this analysis, multimodal imaging was capable of detecting risk factors for nevus transformation into melanoma, including thickness >2 mm (US), fluid subretinal (OCT), symptoms vision loss (Snellen acuity), orange pigment (AF), melanoma hollowness (US), and diameter >5 mm (photography). Increasing number of risk factors imparts greater risk for nevus transformation into melanoma, including thickness >2 mm (US), fluid subretinal (OCT), symptoms vision loss (Snellen acuity), orange pigment (AF), melanoma hollowness (US), and diameter >5 mm (photography). Increasing number of risk factors imparts greater risk for transformation.

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CHOROIDAL NEVUS TRANSFORMATION INTO MELANOMA PER MILLIMETER INCREMENT IN THICKNESS USING MULTIMODAL IMAGING IN 2355 CASES: The 2019 Wendell L. Hughes Lecture
Shields, Carol L.; Dalvin, Lauren A.; Yu, Michael D.; More
RETINA. 39(10):1852-1860, October 2019.

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Purpose:
To analyze risk of nevus transformation into melanoma per millimeter increment.

Methods:
Retrospective analysis of 3,806 choroidal nevi for transformation into melanoma per incremental millimeter thickness (flat [≤1.0 mm], thin [1.1–2.0 mm], thicker [2.1–3.0 mm], and thickest [>3.0 mm])

Results:
The median nevus thickness was 1.4 mm, and nevi were categorized (flat, thin, thicker, and thickest) in 1,140 (30%), 2052 (54%), 555 (15%), and 59 (<1%), respectively. There were differences in tumor diameter (2.5, 4.8, 7.5, and 9.3 mm; P < 0.01), optical coherence tomography detection of overlying subretinal fluid (<1, 4, 15, and 11%; P < 0.01), overlying retinal edema (<1, 3, 14, and 25%; P < 0.01), overlying drusen (23, 49, 64, and 64%; P < 0.01), overlying retinal pigment epithelial detachment (1, 4, 4, and 9%; P < 0.01), and overlying lipofuscin hyperautofluoresence (<1, 3, 6, and 7%; P < 0.01). Choroidal nevus transformation into melanoma (n = 90/2,355 cases, 3.8%) was found by Kaplan–Meier 7-year estimates (2.2, 6.1, 31.7, and 34.5%; P < 0.0001) and by hazard ratio (HR) compared with nevus ≤1.0 mm (not available, 4.7 [ P = 0.01], 35.7 [ P < 0.0001], and 52.0 [ P < 0.0001]). For all thicknesses, those with growth displayed increase in mean basal diameter of 2.4 mm and thickness of 1.1 mm, optical coherence tomography increase in subretinal fluid (65%), autofluorescence increase in lipofuscin (40%), and ultrasonography increase in hollowness (30%). Multivariable risk factors, recalled by the mnemonic “To Find Small Ocular Melanoma Doing IMaging” (TFSOM-DIM) representing Thickness >2 mm (ultrasonography), Fluid subretinal (optical coherence tomography), Symptom vision loss (Va), Orange pigment (autofluorescence), Melanoma hollow (ultrasonography), and DIaMeter >5 mm, revealed factors per incremental thickness category (compared with flat) including thin (Fluid overlying, HR 6.1; DIaMeter >5 mm, HR 3.3), thicker (Fluid subretinal ≤3 mm from nevus, HR 5.7; Melanoma acoustic hollowness, HR 2.7), and thickest (Orange pigment, HR 9.1).

Conclusion:
Each incremental increase in choroidal nevus thickness demonstrated risk of growth into melanoma with HR (compared with flat) 4.7 for thin, 35.7 for thicker, and 52.0 for thickest. The increase from ≤2.0 mm to >2.0 mm thickness conferred the greatest rise for transformation.

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ULTRA-WIDEFIELD MULTIMODAL IMAGING OF PRIMARY VITREORETINAL LYMPHOMA
Lavine, Jeremy A.; Singh, Arun D.; Sharma, Sumit; More
RETINA. 39(10):1861-1871, October 2019.

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Purpose:
To determine the features of primary vitreoretinal lymphoma on multimodal ultra-widefield imaging and correlate these findings to clinical outcomes.

Methods:
We report a retrospective, observational case series of 43 eyes of 23 patients with biopsy-proven B-cell primary vitreoretinal lymphoma. Fundus photography, fluorescein angiography (FA), optical coherence tomography, fundus autofluorescence, and indocyanine green angiography images were reviewed. Medical records were assessed for the central nervous system involvement and visual acuity outcomes at 6 and 12 months after presentation.

Results:
Common fundus photography findings were sub–retinal pigment epithelium lesions and vitritis alone. Common ultra-widefield FA findings were vascular leakage and scleral staining. Retinal optical coherence tomography features overlying sub–retinal pigment epithelium lesions or within the macula predicted fluorescence patterns. The presence of retinal fluid or disorganization associated with hyperfluorescence and late leakage. Normal retinal structures associated with hypofluorescence of sub–retinal pigment epithelium lesions or macular leopard spotting on FA and fundus autofluorescence. Peripheral abnormalities noted on ultra-widefield fundus photography, FA, and indocyanine green angiography were more frequent than posterior pole abnormalities. No imaging characteristics predicted time to the central nervous system progression.

Conclusion:
Ultra-widefield imaging was more informative than posterior pole imaging in fundus photography, FA, and indocyanine green angiography. Common findings on multimodal ultra-widefield imaging may lead to early diagnostic vitrectomy and may reduce the delay in primary vitreoretinal lymphoma diagnosis.

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FULL DIAGNOSTIC VITRECTOMY WITH POSTERIOR VITREOUS DETACHMENT INDUCTION FOR THE DIAGNOSIS OF VITRITIS DUE TO UNCERTAIN ETIOLOGY
Patel, Darshak S.; Khan, Imran J.; Zayed, Mohammed G.; More
RETINA. 39(10):1872-1879, October 2019.

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Purpose:
To report on the diagnostic outcomes and safety of full diagnostic vitrectomy (FDV) with surgical posterior vitreous detachment induction for diagnosing vitritis of uncertain etiology.

Methods:
Forty-nine patients underwent primary FDV using the cassette washings for histopathological analysis. In addition, an undiluted core vitreous sample was obtained for microbial analysis in suspected infective cases. Cases were retrospectively given a diagnosis of inflammatory, infective, or neoplastic based on the results at final follow-up and the outcome of primary FDV categorized as diagnostic or nondiagnostic. The success of FDV was evaluated in relation to the final diagnosis. The need for additional intraocular biopsies and intraoperative or postoperative complications was also recorded.

Results:
Full diagnostic vitrectomy was diagnostic in 26/49 cases (53%) and nondiagnostic in 23 (47%). The diagnostic success rate was greatest in neoplastic (16/20, 80%) and infective cases (9/13, 69%). Seven cases (14%) required additional biopsies to establish the diagnosis, and in 15/49 cases (31%), no cause of vitritis was identified. Intraoperative retinal breaks occurred in 3/49 cases (6%) and retinal detachment in 1/49 cases (2%). Three of 49 cases (6%) developed transiently elevated intraocular pressure postoperatively.

Conclusion:
Full diagnostic vitrectomy in combination with an undiluted core vitreous biopsy for suspected infections is safe and effective at securing a diagnosis in vitritis, particularly in cases of neoplasia.

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SUPRACHOROIDAL INJECTION OF TRIAMCINOLONE ACETONIDE, CLS-TA, FOR MACULAR EDEMA DUE TO NONINFECTIOUS UVEITIS: A Randomized, Phase 2 Study (DOGWOOD)
Yeh, Steven; Kurup, Shree K.; Wang, Robert C.; More
RETINA. 39(10):1880-1888, October 2019.

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Purpose:
Evaluate a single suprachoroidal injection of a proprietary triamcinolone acetonide suspension, CLS-TA, in subjects with macular edema due to noninfectious uveitis.

Methods:
Randomized, controlled, masked Phase 2 study. Safety and efficacy of a single suprachoroidal injection of CLS-TA (4.0 and 0.8 mg in a 4:1 ratio) were assessed at 1 and 2 months after injection. The primary efficacy endpoint was change in central subfield thickness from baseline to Month 2, assessed by spectral domain optical coherence tomography.

Results:
Twenty-two adults were enrolled. The primary endpoint was met in subjects who received suprachoroidal injection of CLS-TA 4.0 mg, mean central subfield thickness significantly decreased from baseline by 135 µ m and 164 µ m at Month 1 ( P = 0.0056) and Month 2 ( P = 0.0017), respectively. At Month 2, 69% of subjects who received 4.0 mg experienced ≥20% reduction in central subfield thickness, and 65% had improvement of best-corrected visual acuity of ≥5 Early Treatment Diabetic Retinopathy Study letters, with a mean improvement of 9.2 letters ( P = 0.0004). Safety analyses supported acceptable safety/tolerability, with no corticosteroid-related increases in intraocular pressure.

Conclusion:
A single suprachoroidal injection of CLS-TA (4.0 mg; 0.1 mL) in subjects with macular edema due to noninfectious uveitis was well-tolerated, significantly reduced central subfield thickness from baseline at 2 months, and significantly improved visual acuity.

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RETINAL CAPILLARY MACROANEURYSMS
Spaide, Richard F.; Barquet, Luis Arias
RETINA. 39(10):1889-1895, October 2019.

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Purpose:
To investigate eyes with solitary large aneurysms arising from retinal capillaries.

Methods:
Consecutive patients with aneurysms greater than 200 µ m in diameter were evaluated with a comprehensive ophthalmologic examination including optical coherence tomography, optical coherence tomography angiography, and fluorescein angiography. The aneurysms were solitary in the sense, and there was only one aneurysm larger than the threshold diameter and a few or no other aneurysms.

Results:
There were 5 patients, 3 male patients, who had aneurysms that reached a maximal mean size of 273.4 µ m. One patient had stable diabetic retinopathy and had a documented growth of a capillary aneurysm to 331 µ m over an 8-year 7-month period until the aneurysm was associated with widespread edema. The remaining 4 patients did not have diabetes or any discernable retinal vascular disease. Anti–vascular endothelial growth factor treatment was associated with a partial response in one patient and no apparent response in the others. Laser photocoagulation of the aneurysms resulted in resolution of the edema and involution of the lesions.

Conclusion:
Large aneurysms arising from retinal capillaries occur and have a candidate name of retinal capillary macroaneurysms. Histologic evaluation of retinal capillary aneurysms shows the presence of matrix metalloproteinase-9, which may function to decrease the wall strength in the face of increasing wall tension from aneurysmal expansion, as predicted by LaPlace's law. Thus, retinal capillary macroaneurysms may have multiple forces driving their formation.

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FIXATION STATUS AFTER RESOLUTION OF MACULAR EDEMA ASSOCIATED WITH BRANCH RETINAL VEIN OCCLUSION
Kogo, Takahiro; Muraoka, Yuki; Ooto, Sotaro; More
RETINA. 39(10):1896-1905, October 2019.

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Purpose:
To evaluate fixation status of eyes with branch retinal vein occlusion (BRVO) and to investigate its association with other clinical parameters.

Methods:
This study included 57 consecutive eyes with BRVO after resolution of macular edema. Fixation status was determined by microperimetry. Defect length of the foveal ellipsoid zone band was measured by optical coherence tomography, and retinal perfusion status was assessed by optical coherence tomography angiography.

Results:
In microperimetry, the mean fixation rate around the gravitational center of all fixation points (defined as the fixation center) was found to be 79.8 ± 18.9%, which was significantly associated with defect length of the foveal ellipsoid zone band ( P < 0.001) and distance between the foveal and fixation centers ( P = 0.012). The integrity of the ellipsoid zone band at the fixation center was intact in 55 eyes (96.5%). Fixation centers were located within and outside the foveal avascular zone in 33 (57.9%) and 24 (42.1%) eyes, respectively; among the latter eyes, all fixation centers were perfused. Downward deviation of fixation points was rare, despite variations in the occluded area; there was a significant difference in distribution of deviation between eyes with superotemporal and inferotemporal BRVO ( P < 0.001).

Conclusion:
In eyes with BRVO, fixation status was strongly associated with visual acuity, morphologic damage, and retinal perfusion status both in the foveal area and at the fixation center after resolution of macular edema. This information regarding fixation status could facilitate vision management in patients with BRVO.

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NOVEL OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY BIOMARKER IN BRANCH RETINAL VEIN OCCLUSION MACULAR EDEMA
Yeung, Ling; Wu, Wei-Chi; Chuang, Lan-Hsin; More
RETINA. 39(10):1906-1916, October 2019.

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Purpose:
To evaluate the association between deep–superficial flow ratio (DSFR) and the treatment response of macular edema in branch retinal vein occlusion.

Methods:
Thirty eyes from 30 patients with branch retinal vein occlusion who had received optical coherence tomography angiography examination were included. Seventeen normal fellow eyes acted as the control group. Patients were classified into the “good response group” and the “refractory group” by absence or presence of macular edema after 6 months of treatment. The DSFRs were calculated by dividing deep capillary plexus vessel density by superficial capillary plexus vessel density on optical coherence tomography angiography.

Results:
The DSFR was 1.00 (SD ± 0.05) over parafoveal area in the control group. Among branch retinal vein occlusion eyes, parafoveal DSFR remained stable in the good response group ( P = 0.822) and significantly decreased in the refractory group ( P = 0.002). The DSFRs in the most severe nonperfusion area were significantly lower in the refractory group than in the good response group (0.85 ± 0.13 vs. 1.01 ± 0.15, P = 0.004). The DSFR in the most severe nonperfusion area was associates with treatment response in multivariate logistic regression ( P = 0.015).

Conclusion:
Deep–superficial flow ratio can represent the relative damage of deep capillary plexus to superficial capillary plexus. Decreased DSFR was found in branch retinal vein occlusion eyes with refractory macular edema.

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CENTRAL RETINAL VEIN OCCLUSION IN YOUNG INDIVIDUALS: A Comparison of Risk Factors and Clinical Outcomes
Rothman, Adam L.; Thomas, Akshay S.; Khan, Kirin; More
RETINA. 39(10):1917-1924, October 2019.

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Purpose:
To compare the presentation and outcomes of patients younger than 50 years versus patients aged 50 years and older with central retinal vein occlusion (CRVO).

Methods:
This single-center retrospective study included patients with CRVO presenting between January 2009 and July 2016. Charts were reviewed and data were abstracted. Presenting and final clinical parameters, treatment burden, and predisposing factors for CRVO were compared between the two groups.

Results:
Thirty-six patients younger than 50 years and 233 patients aged 50 years and older at the time of CRVO onset were included. At presentation, younger patients had better visual acuity than older patients (20/80 vs. 20/224, P = 0.001) and a lower incidence of cystoid macular edema (54 vs. 79%, P = 0.001). Twenty-one of 36 (58%) younger patients had at least one identifiable nontraditional risk factor for CRVO. At final follow-up, younger patients received fewer total intravitreal injections (3.8 ± 5.8 at 34.2 months) compared with older patients (6.5 ± 8.8, at 37.6 months, P = 0.03) and had better final acuity (20/85 vs. 20/289, P = 0.004, respectively).

Conclusion:
Younger patients had better baseline and final acuities, a lower incidence of cystoid macular edema at presentation, and received fewer intravitreal injections than older patients. Workup for etiology of CRVO in younger patients may reveal nontraditional risk factors for CRVO.

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SPECKLED HYPOAUTOFLUORESCENCE AS A SIGN OF RESOLVED SUBRETINAL HEMORRHAGE IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION
Hussnain, S. Amal; Dolz-Marco, Rosa; Dunaief, Joshua L.; More
RETINA. 39(10):1925-1935, October 2019.

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Purpose:
To describe patterns of hypoautofluorescence in eyes with neovascular age-related macular degeneration occurring after subretinal hemorrhage.

Methods:
This was a retrospective descriptive analysis of neovascular age-related macular degeneration eyes presenting with subretinal hemorrhage over the last 5 years that underwent serial multimodal imaging. A review of color fundus photographs, fundus autofluorescence, near-infrared reflectance, and optical coherence tomography was performed at baseline and all available follow-up visits to document the course and evolution of subretinal hemorrhage in these eyes.

Results:
Eleven eyes of 10 patients (9 female, 1 male; mean age: 84.1 years, range: 72–99 years) with a mean follow-up of 19.8 months (range: 3–68 months) were included. Color fundus photographs showed subretinal hemorrhage that resolved over a mean of 5.5 months. During and after hemorrhage resolution, all eyes showed hypoautofluorescence, which appeared distinct from that due to retinal pigment epithelium loss. Discrete multifocal punctate hyperpigmented lesions were observed in 90% of eyes and were markedly hypoautofluorescent, producing a speckled pattern on fundus autofluorescence.

Conclusion:
Areas of hypoautofluorescence in the absence of retinal pigment epithelium atrophy, often with a speckled pattern, delineate areas of prior subretinal hemorrhage long after its resolution in patients with neovascular age-related macular degeneration. Potential mechanisms for the development of this pattern are proposed.

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AGE-RELATED MACULAR DEGENERATION–ASSOCIATED PERIPAPILLARY CHOROIDAL NEOVASCULARIZATION IN THE ERA OF ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY
Lin, Tiezhu; Dans, Kunny; Meshi, Amit; More
RETINA. 39(10):1936-1944, October 2019.

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Purpose:
To characterize the natural history and response of age-related macular degeneration–associated peripapillary choroidal neovascularization to anti–vascular endothelial growth factor therapy.

Methods:
This was a retrospective case series of patients with peripapillary choroidal neovascularization secondary to neovascular age-related macular degeneration. All patients underwent complete ophthalmologic examination and retinal imaging including fluorescein angiography and spectral domain optical coherence tomography at each visit. Eyes with subretinal or intraretinal macular fluid were treated with anti–vascular endothelial growth factor monotherapy using a modified as-needed treatment algorithm.

Results:
Thirty-three eyes of 27 patients were included. The median age was 82 years (range, 62–94), and the median duration of follow-up was 65 months (range, 6–165). Fourteen eyes (58%) without fovea-involving fluid at baseline subsequently developed exudation after a median observation period of 16 months (range, 4–107). Ten of 24 eyes (42%) without initial macular fluid remained dry during the entire follow-up. The median number of injections required until complete fluid reabsorption was 3 (range, 1–21) during the first treatment cycle. The median time to fluid recurrence was 6 months (range, 3–74).

Conclusion:
Peripapillary choroidal neovascularization secondary to wet age-related macular degeneration has a slow progression, may not require treatment for a prolonged period, and responds rapidly to anti–vascular endothelial growth factor treatment with good visual outcomes.

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INCIDENCE OF LATE AGE-RELATED MACULAR DEGENERATION IN EYES WITH RETICULAR PSEUDODRUSEN
Kong, Mingui; Kim, Sungmin; Ham, Don-Il
RETINA. 39(10):1945-1952, October 2019.

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Purpose:
To investigate the incidence of late age-related macular degeneration (AMD) over 3 years and risk factors for the development of late AMD in Korean patients having reticular pseudodrusen (RPD).

Methods:
Clinical records of Korean RPD patients with no late AMD at first examination and completion of 3 years of regular follow-up were retrospectively reviewed. All patients underwent complete ocular examinations, including multimodal imaging. Reticular pseudodrusen were classified as a separate lesion different from other early AMD lesions, and RPD were not considered a sign of early AMD. Risk factors for the development of late AMD were assessed.

Results:
One hundred and ninety-two RPD eyes of 104 patients were included in this study. Mean age of patients was 69.4 ± 8.9 years, and other early AMD lesions were accompanied in 152 eyes (79.2%) at baseline. During 3 years, late AMD occurred in 30 eyes (15.6%); geographic atrophy in 24 eyes (12.5%); and neovascular AMD in 6 eyes (3.1%). Eyes having early AMD at baseline revealed significantly higher incidence for late AMD than those eyes having no early AMD at baseline (18.4% vs. 5%, P = 0.048). Late AMD occurred in 5 eyes (38.5%) from 13 fellow RPD eyes of unilateral late AMD at baseline. In logistic regression analysis, thin choroidal thickness, diffuse distribution of RPD, and the presence of late AMD on fellow eye at baseline were significant risk factors for developing late AMD in RPD eyes.

Conclusion:
Reticular pseudodrusen eyes revealed various progression rates to late AMD according to AMD status of both eyes. More frequent monitoring should be considered for patients with RPD at risk of progression to late AMD.

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EFFICACY OF ADJUVANT TOPICAL DORZOLAMIDE–TIMOLOL IN PATIENTS WITH NEOVASCULAR AGE-RELATED MACULAR DEGENERATION REFRACTORY TO ANTI–VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY
Lee, Ji Hwan; Lee, Sung Chul; Byeon, Suk Ho; More
RETINA. 39(10):1953-1958, October 2019.

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Purpose:
To evaluate the efficacy of adjuvant topical dorzolamide–timolol in patients with neovascular age-related macular degeneration unresponsive to anti–vascular endothelial growth factor therapy.

Methods:
This retrospective, interventional study included 15 patients with neovascular age-related macular degeneration refractory to anti–vascular endothelial growth factor. Patients used topical dorzolamide–timolol twice daily in the neovascular age-related macular degeneration eye and received anti–vascular endothelial growth factor therapy at each visit, with the same fixed interval and agent as before the addition of dorzolamide–timolol. Central macular thickness, maximal subretinal fluid height, and maximal pigment epithelial detachment height were measured at baseline and every visit.

Results:
The mean follow-up period was 17.2 ± 5.5 weeks. The mean central macular thickness decreased from 383.5 μ m at baseline to 298.3 μ m at the final visit ( P = 0.041). The mean maximal subretinal fluid height decreased from 105.0 μ m at baseline to 58.3 μ m at the final visit ( P = 0.021). Complete resolution of subretinal fluid was observed in 3 of 11 subretinal fluid–type eyes. There was no significant change in the maximal pigment epithelial detachment height. The mean logarithm of the minimum angle of resolution visual acuity decreased from 0.61 (20/81 Snellen) at baseline to 0.66 (20/91 Snellen) at final visit, which was not significant ( P = 0.314). The mean intraocular pressure decreased significantly from 14.9 mmHg at baseline to 12.3 mmHg at the final visit ( P = 0.005).

Conclusion:
The use of adjuvant topical dorzolamide–timolol was effective in decreasing central macular thickness and subretinal fluid in patients with neovascular age-related macular degeneration refractory to continual fixed-interval intravitreal anti–vascular endothelial growth factor therapy, but did not result in functional improvement in this short-term study.

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EFFECT OF SERIAL ANTERIOR CHAMBER PARACENTESIS ON SUSTAINED INTRAOCULAR PRESSURE ELEVATION IN PATIENTS RECEIVING INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR THERAPY
Sisk, Robert A.; Rusia, Deepam; Zamora, Brian G.; More
RETINA. 39(10):1959-1964, October 2019.

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Purpose:
To investigate the effect of serial anterior chamber (AC) paracenteses in eyes with sustained elevations of intraocular pressure (IOP) in the setting of repeated intravitreal injections (IVI) of anti–vascular endothelial growth factor medications.

Methods:
This is a retrospective records review of patients undergoing IVI of anti–vascular endothelial growth factor medication (bevacizumab, ranubizumab, or aflibercept), who demonstrated a sustained elevation of preinjection IOP and also received AC paracentesis immediately after IVI on at least three consecutive visits. Changes in preinjection IOP and cup-to-disk (C:D) ratio were compared before and after the initiation of IVI and before and after the introduction of AC paracenteses with each subsequent IVI.

Results:
Twenty-three eyes of 17 patients receiving a median of 26 IVI experienced a rise in preinjection IOP from 16.3 mmHg to 21.1 mmHg ( P = 0.004) and an increase in mean C:D ratio from 0.37 to 0.47 ( P = 0.0002). After introduction of AC paracenteses (median of 12), mean IOP was returned to baseline 16.00 mmHg ( P = 0.002), mean C:D ratio stabilized (0.50, P = 0.197), and maximum IOP decreased from 26.8 mmHg to 23.0 mmHg ( P = 0.05). Nineteen (82.6%) eyes required an increase in topical glaucoma medications during the study period, and 13 (56.5%) still required additional therapies after initiation of AC paracenteses. Five eyes (38.5%) required laser or glaucoma drainage device procedures.

Conclusion:
Serial AC paracenteses reduced immediate postinjection IOP, and along with standard glaucoma care in most patients, reversed preinjection IOP elevation, and stabilized optic nerve changes associated with repeated intravitreal anti–vascular endothelial growth factor injections in a subset of patients with sustained elevation of preinjection IOP.

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ASSOCIATION BETWEEN ORAL IRON SUPPLEMENTATION AND RETINAL OR SUBRETINAL HEMORRHAGE IN THE COMPARISON OF AGE-RELATED MACULAR DEGENERATION TREATMENT TRIALS
Song, Delu; Ying, Gui-Shuang; Dunaief, Joshua L.; More
RETINA. 39(10):1965-1972, October 2019.

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Purpose:
Because patients often take iron supplements without medical indication, and iron can accumulate in vascular endothelial cells, the authors evaluated the association of oral iron supplementation with retinal/subretinal hemorrhage in patients with neovascular age-related macular degeneration.

Methods:
A post hoc secondary data analysis of comparison of age-related macular degeneration treatments trials was performed. Participants were interviewed for use of oral iron supplements. Trained readers evaluated retinal/subretinal hemorrhage in baseline fundus photographs. Adjusted odds ratios from multivariate logistic regression models assessed the association between iron use and baseline hemorrhage adjusted by age, sex, smoking, hypertension, anemia, and use of antiplatelet/anticoagulant drugs.

Results:
Among 1,165 participants, baseline retinal/subretinal hemorrhage was present in the study eye in 71% of 181 iron users and in 61% of 984 participants without iron use (adjusted odds ratio = 1.47, P = 0.04), and the association was dose dependent (adjusted linear trend P = 0.048). Iron use was associated with hemorrhage in participants with hypertension (adjusted odds ratio = 1.87, P = 0.006) but not without hypertension. The association of iron use with hemorrhage remained significant among hypertensive participants without anemia (adjusted odds ratio = 1.85, P = 0.02).

Conclusion:
Among participants of comparison of age-related macular degeneration treatments trials, the use of oral iron supplements was associated with retinal/subretinal hemorrhage in a dose–response manner. Unindicated iron supplementation may be detrimental in patients with wet age-related macular degeneration.

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SENSITIVITY OF 840-nm SPECTRAL DOMAIN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN DETECTING TYPE 1 NEOVASCULARIZATION ACCORDING TO THE HEIGHT OF THE ASSOCIATED PIGMENT EPITHELIAL DETACHMENT
Mrejen, Sarah; Giocanti-Auregan, Audrey; Tabary, Sandrine; More
RETINA. 39(10):1973-1984, October 2019.

Abstract
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Purpose:
To evaluate the ability of optical coherence tomography angiography (OCTA) to detect abnormal vascular blood flow in Type 1 neovascularization (NV) with or without significant pigment epithelial detachment (PED).

Methods:
Consecutive age-related macular degeneration patients with either treatment-naive or anti–vascular endothelial growth factor–treated Type 1 NV were divided into 2 groups based on the PED height on structural OCT: greater than 250 μ m (Group 1) versus less than 250 μ m (Group 2). Two independent senior retina specialists analyzed the OCTA images (Zeiss Angioplex OCT, Carl Zeiss AG, Jena, Germany) using the automatic slabs alone (first reader) versus automatic and manual segmentation slabs (second reader).

Results:
In Group 1, 15 men and 42 women, aged from 51 years to 97 years (mean: 87.5), were included. Optical coherence tomography angiography was able to show an abnormal blood flow suggestive of Type 1 NV in 23 (40.3%) of 57 eyes for the first reader and in 32 (56.1%) of 57 eyes for the second reader. In Group 2, 7 men and 30 women, aged from 60 years to 96 years (mean: 80.2), were included. The first and second readers were able to observe an image suggestive of Type 1 NV in 33/37 (89.2%) and 37/37 (100%) of eyes, respectively.

Conclusion:
The ability of OCTA to detect an abnormal blood flow in Type 1 NV was found to highly depend on the height of the associated PED and the use of manual segmentation slabs. Our results suggest that automatic slabs of OCTA should be interpreted with caution for the diagnosis of vascularized PED. The diagnosis of Type 1 NV using OCTA requires the use of manual segmentation and a multimodal imaging approach, especially when the height of the associated PED is >250 μ m.

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RANIBIZUMAB VERSUS VERTEPORFIN PHOTODYNAMIC THERAPY IN ASIAN PATIENTS WITH MYOPIC CHOROIDAL NEOVASCULARIZATION: BRILLIANCE, a 12-Month, Randomized, Double-Masked Study
Chen, Youxin; Sharma, Tarun; Li, Xiaorong; More
RETINA. 39(10):1985-1994, October 2019.

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Purpose:
To evaluate the efficacy and safety of 2 dosing regimens of ranibizumab 0.5 mg versus verteporfin photodynamic therapy in Asian patients with visual impairment due to myopic choroidal neovascularization.

Methods:
Eligible patients (aged ≥18 years) were randomized 2:2:1 to Group I (n = 182; ranibizumab treatment guided by visual acuity stabilization criteria); Group II (n = 184; ranibizumab treatment guided by disease activity); or Group III (n = 91; verteporfin photodynamic therapy on Day 1; from Month 3, ranibizumab/verteporfin photodynamic therapy/both treatment guided by disease activity).

Results:
The mean average best-corrected visual acuity change from baseline to Month 1 through Month 3 was significantly higher in Groups I/II versus Group III (Group I/II: +9.5/+9.8 letters vs. Group III: +4.5 letters; both P < 0.001). Group II was statistically noninferior to Group I for the mean average best-corrected visual acuity change from baseline to Month 1 through Month 6 (10.7 vs. 10.4 letters; P < 0.001). Over 12 months, the mean number of ranibizumab injections received by Groups I/II/III was 4.6/3.9/3.2.

Conclusion:
In Asian patients, ranibizumab treatments demonstrated superior efficacy versus verteporfin photodynamic therapy at Month 3, and the beneficial treatment effects persisted at Month 12. Ranibizumab was well-tolerated and demonstrated a good safety profile.

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TYPICAL POLYPOIDAL CHOROIDAL VASCULOPATHY AND POLYPOIDAL CHOROIDAL NEOVASCULARIZATION
Jang, Jun Won; Kim, Jong Min; Kang, Se Woong; More
RETINA. 39(10):1995-2003, October 2019.

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Purpose:
To compare typical polypoidal choroidal vasculopathy (T-PCV) and polypoidal choroidal neovascularization (P-CNV), which can be defined as two subtypes of PCV, and to elucidate the significance of the classification.

Methods:
Seventy-seven patients diagnosed with PCV and followed up for more than 12 months were reviewed. The PCV cases were divided into a T-PCV group (n = 36) and a P-CNV group (n = 41) according to the presence of features of pachychoroid or age-related macular degeneration. Angiographic and tomographic characteristics and changes in vision during the follow-up period were compared between the two groups.

Results:
Logarithm of the minimum angle of resolution visual acuity of T-PCV and P-CNV was 0.27 ± 0.31 and 0.62 ± 0.47 at baseline ( P < 0.001) and 0.28 ± 0.41 and 0.54 ± 0.52 at the final visit ( P = 0.006), respectively. A marginally higher rate of complete response to anti–vascular endothelial growth factor treatment was noted in the T-PCV group (47.2%) compared with the P-CNV group (26.8%) ( P = 0.05). At the final visit, subfoveal fibrosis was noted in 11.1% of the T-PCV group and 39.0% of the P-CNV group ( P = 0.009).

Conclusion:
The two subtypes of PCV, P-CNV and T-PCV, behave differently in terms of angiographic and tomographic manifestations and visual outcomes. Classifying PCVs would be helpful not only for pathogenic implications, but also for prognostic significance.

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COMPARATIVE RISK OF ENDOPHTHALMITIS AFTER INTRAVITREAL INJECTION WITH BEVACIZUMAB, AFLIBERCEPT, AND RANIBIZUMAB
Bavinger, J. Clay; Yu, Yinxi; VanderBeek, Brian L.
RETINA. 39(10):2004-2011, October 2019.

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Purpose:
To determine whether sterile preloading of anti–vascular endothelial growth factor agents reduces the risk of postintravitreal injection endophthalmitis.

Methods:
This is a retrospective cohort study using medical claims data from a large, national US insurer. Cohorts were created using intravitreal injections of anti–vascular endothelial growth factor injections from 2005 to 2016. For inclusion, patients had to have at least 6 months of data before the injection and were excluded for any previous diagnosis of endophthalmitis, multiple injected drugs on the day of injection, or intraocular surgery within 15 days of the injection or between an injection and a diagnosis of endophthalmitis. The primary outcome was the odds of endophthalmitis after an intravitreal injection.

Results:
A total of 706,725 bevacizumab, 210,849 ranibizumab, and 177,731 aflibercept injections were given to 130,327 patients. Multivariate analysis showed that ranibizumab and aflibercept together had an increased odds of endophthalmitis (odds ratio = 1.29, 95% confidence interval: 1.04–1.59, P = 0.02) compared with bevacizumab. Individually, ranibizumab (odds ratio = 1.25, 95% confidence interval: 0.97–1.61, P = 0.08) and aflibercept (odds ratio = 1.34, 95% confidence interval: 0.99–1.81, P = 0.06) each had higher odds of endophthalmitis, but neither result met significance. Also, when compared with male patients, female patients had a higher odds of getting endophthalmitis (odds ratio: 1.30, 95% confidence interval: 1.05–1.61, P = 0.02).

Conclusion:
The odds of endophthalmitis with aflibercept and ranibizumab combined were higher compared with the sterilely preloaded bevacizumab, arguing for a safety advantage of sterile preloading of anti–vascular endothelial growth factor injections.