Late-Onset Retinal Findings and Complications in Untreated Retinopathy of Prematurity.

PURPOSE: To investigate late retinal findings and complications of eyes with a history of retinopathy of prematurity (ROP) that did not meet treatment criteria and did not receive treatment during infancy. DESIGN: Retrospective, nonconsecutive, noncomparative, multicenter case series. PARTICIPANTS: Three hundred sixty-three eyes of 186 patients. METHODS: Data were requested from multiple providers on premature patients with a history of ROP and no treatment during infancy who demonstrated late retinal findings or complications and included age, gender, gestational age and weight, zone and stage at infancy, visual acuity, current retina vascularization status, vitreous character, presence of peripheral retinal findings such as lattice retinal tears and detachments (RDs), retinoschisis, and fluorescein findings. MAIN OUTCOME MEASURES: Rate of RDs and factors conferring a higher risk of RDs. RESULTS: The average age was 34.5 years (range, 7-76 years), average gestational age was 26.6 weeks (range, 23-34 weeks), and average birth weight was 875 g (range, 425-1590 g). Findings included lattice in 196 eyes (54.0%), atrophic holes in 126 eyes (34.7%), retinal tears in 111 eyes (30.6%), RDs in 140 eyes (38.6 %), tractional retinoschisis in 44 eyes (11.9%), and visible vitreous condensation ridge-like interface in 112 eyes (30.5%). Fluorescein angiography (FA) was performed in 113 eyes, of which 59 eyes (52.2%) showed leakage and 16 eyes (14.2%) showed neovascularization. Incomplete vascularization posterior to zone 3 was common (71.6% of eyes). Retinal detachments were more likely in patients with a gestational age of 29 weeks or less (P < 0.05) and in eyes with furthest vascularization to posterior zone 2 eyes compared with zone 3 eyes (P = 0.009). CONCLUSIONS: Eyes with ROP not meeting the treatment threshold during infancy showed various late retinal findings and complications, of which RDs were the most concerning. Complications were seen in all age groups, including patients born after the Early Treatment for Retinopathy of Prematurity Study. Contributing factors to RDs included atrophic holes within peripheral avascular retina, visible vitreous condensation ridge-like interface with residual traction, and premature vitreous syneresis. We recommend regular examinations and consideration of ultra-widefield FA examinations. Prospective studies are needed to explore the frequency of complications and benefit of prophylactic treatment and if eyes treated with anti-vascular endothelial growth factor therapy are at risk of similar findings and complications.

Imaging of Hydroxychloroquine Toxicity with Fluorescence Lifetime Imaging Ophthalmoscopy.

PURPOSE: To investigate the impact of retinal toxicity from hydroxychloroquine (HCQ) on fundus autofluorescence lifetimes using fluorescence lifetime imaging ophthalmoscopy (FLIO). DESIGN: Cross-sectional study. PARTICIPANTS: Twenty-four eyes of 12 patients with definite HCQ toxicity, 31 eyes of 16 clinically normal patients at high risk of developing HCQ toxicity (taking HCQ longer than 5 years), and 16 eyes of 8 clinically normal patients at low risk of developing HCQ toxicity (taking HCQ fewer than 5 years), as well as 22 age-matched healthy subjects. METHODS: Fluorescence lifetime images of a 30° retinal field centered at the fovea were collected at the Moran Eye Center, Salt Lake City, Utah. A prototype Heidelberg Engineering Spectralis-based FLIO was used to detect autofluorescence lifetimes in short (SSC; 498-560 nm) and long (LSC; 560-720 nm) spectral channels. Mean fluorescence lifetimes were calculated. OCT scans and macular pigment measures were also recorded. Additionally, the autofluorescence lifetimes of HCQ were measured in a cuvette. MAIN OUTCOME MEASURES: Mean autofluorescence lifetimes (τm). RESULTS: All patients with HCQ toxicity showed significantly prolonged FLIO lifetimes in regions of damage, typically in a bulls-eye distribution corresponding to toxic lesions in the retina (SSC: lesion, 400 ps; unremarkable retina, 294 ps; P < 0.001; LSC: lesion, 404 ps; unremarkable retina, 316 ps; P < 0.001). Some clinically normal patients at high risk (9 of 16) and at low risk (2 of 8) of developing HCQ toxicity also showed prolonged FLIO lifetimes in the parafoveal region, whereas age-matched healthy subjects did not. HCQ at a concentration of 46 mM exhibited long autofluorescence lifetimes of around 1100 ps in either spectral channel. CONCLUSIONS: Fluorescence lifetime imaging ophthalmoscopy seems to detect retinal toxicity from HCQ at very early stages and could be a novel method to detect retinal toxicity before irreversible damage is manifest.

Longitudinal Examination of Fellow-Eye Vascular Anomalies in Coats' Disease With Widefield Fluorescein Angiography: A Multicenter Study.

BACKGROUND AND OBJECTIVE: Retinovascular anomalies in the fellow eyes of patients with Coats' disease have been described, but the clinical significance is unknown, as well as whether these lesions progress over time. PATIENTS AND METHODS: This is an international, multicenter, retrospective, observational cohort study of fellow-eye abnormalities on widefield fluorescein angiography in patients with Coats' disease. RESULTS: Three hundred fifty eyes of 175 patients with Coats' disease were analyzed. A total of 33 patients (18.8%) demonstrated abnormal fellow-eye findings: 14 (42.4%) telangiectasias, 18 (54.5%) aneurysms, six (18.2%) segmental non-perfusion, six (18.2%) leakage, and two (6.0%) vascular tortuosity. All eyes were asymptomatic, and none of the lesions progressed over time. There was no association between fellow-eye findings with severity of Coats' disease (P = .16), patient age (P = .16), or presence of systemic vascular disease (P = .16). CONCLUSIONS: The vascular abnormalities in fellow eyes of patients with Coats' disease did not progress over time. Observation is a reasonable initial management strategy. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:221-227.].

Genetic Penetrance of Macular Telangiectasia Type 2.

Importance: The apparent genetic penetrance of macular telangiectasia type 2 (MacTel) is important for gene discovery studies and for clinical risk assessment of affected individuals' family members. Objective: To determine the genetic penetrance of MacTel. Design, Setting, and Participants: Descriptive cross-sectional study of patients with MacTel at a tertiary referral eye center. From 2008 to 2016, consecutive patients with MacTel were independently identified, and all of their available siblings and parents were recruited. Seventeen probands with MacTel were included in the study who satisfied the requirement of having at least 1 parent or sibling willing and able to participate. Data from these 17 families were included for the analysis of apparent genetic penetrance. Main Outcomes and Measures: Determination of MacTel genetic penetrance in probands' parents and siblings. Results: Of 80 study participants, 50 (62.5%) were women. The mean (SD) age of study participants with MacTel was 61.2 (14.0) years (range, 23-81 years) and without MacTel was 60.7 (16.4) years (range, 24-92 years). There were 17 MacTel probands, and there was a high rate of enrollment of living siblings and parents: 52 of 71 living siblings (73%) and 11 of 12 parents (92%). Of 52 enrolled siblings, 9 (17%) were affected. Of 11 enrolled parents, 3 (27%) had MacTel. Apparent genetic penetrance was calculated to be 0.35 (95% CI, 0.14-0.6) by sibling analysis and 0.55 (95% CI, 0.02-1.00) by parent analysis. Combining the sibling and parent analyses, the apparent penetrance was calculated to be 0.38 (95% CI, 0.19-0.57). Conclusions and Relevance: The genetic penetrance of MacTel in rigorously phenotyped multiple large families is described. Families such as these could be critical for successful identification of MacTel genes.

The utility of ultra-widefield fluorescein angiography in pediatric retinal diseases.

BACKGROUND: Ultra-widefield angiography is the latest technology in the evolution of fundus fluorescein angiography. With the ability to capture up to 200° of the fundus in a single image, far peripheral retinal pathology can be imaged. Generally, obtaining high-quality fundus fluorescein angiography in a child without sedation in the outpatient setting is exceedingly challenging. Therefore, there are advantages to imaging platforms that can capture the peripheral retina in young children without anesthesia. Often pediatric retinal diseases have pathology localized to the far periphery, which further validates the utility of ultra-widefield angiography. Ultra-widefield angiography has been successfully used without sedation for evaluation of children with various pediatric retinal diseases such as Coats disease, familial exudative vitreoretinopathy, and retinopathy of prematurity. CONCLUSION: This non-contact, non-mydriatic modality has been utilized in the evaluation of pediatric retinal diseases and demonstrated to have benefits over conventional fluorescein angiography techniques.

What do we know about the macular pigment in AMD: the past, the present, and the future.

Carotenoids are lipophilic isoprenoid pigments with a common C40H56 core chemical structure that are naturally synthesized by many plants, algae, bacteria, and fungi. Humans and animals cannot synthesize carotenoids de novo and must obtain them solely through dietary sources. Among the more than 750 carotenoids in nature, only lutein, zeaxanthin, meso-zeaxanthin, and their oxidative metabolites selectively accumulate in the foveal region of the retina where they are collectively referred to as the macular pigment (MP) of the macula lutea. MP serves an ocular protective role through its ability to filter phototoxic blue light radiation and also via its antioxidant activity. These properties have led to the hypothesis that carotenoids may protect against the development of age-related macular degeneration (AMD), the most common cause of blindness in the aged population >60 years old. Epidemiological studies have supported this by showing that patients with lower concentrations of serum carotenoids and macular pigment optical density (MPOD) measurements are at a higher risk of developing AMD. Conversely, nutritional supplementation and diets rich in lutein and zeaxanthin readily impact MP concentrations and reduce the risk of progression to advanced AMD, and the AREDS2 supplement formulation containing 10 mg of lutein and 2 mg of zeaxanthin is the standard-of-care recommendation for individuals at risk for visual loss from advanced AMD. This article reviews the rich history of research on the MP dating back to the 1700s and outlines their potential for further therapeutic improvements for AMD in the future.

Correlation of Clinical Outcomes with Quantitative Polymerase Chain Reaction DNA Copy Number in Patients with Acute Retinal Necrosis.

PURPOSE: To correlate visual acuity outcomes and clinical features with quantitative PCR DNA copy number in patients with acute retinal necrosis (ARN). METHODS: Retrospective, consecutive case series. RESULTS: In total, 14 eyes of 13 patients were diagnosed with ARN, based on the American Uveitis Society criteria, and were followed for a mean of 324.5 days (median 250.5 days, SD ± 214 days). Anterior chamber fluid analyzed by quantitative PCR identified viral DNA in 11 of 14 eyes (78.5%). Varicella zoster virus (VZV) was identified in seven eyes (50%) and herpes simplex virus (HSV) in four eyes (28.5%). Mean DNA copy number was 7.9 × 106/mL (median 2.10 × 106/mL, range: 0-5.60 × 107/mL). Eyes with quantitative PCR DNA copy number of ≥5.0 × 106/mL (n = 6 eyes) had worse baseline visual acuity (logMAR 1.48 ± 0.71 vs 0.94 ± 0.76, p = 0.196) and final visual acuity (logMAR 2.10 ± 0.60 vs 0.82 ± 0.81, p = 0.007) compared with patients with a DNA copy number <5.0 × 106/mL (n = 8 eyes). Patients with a DNA copy number of ≥5.0 × 106/mL were more likely to have at least 5 clock hours of retinitis on funduscopic exam (p = 0.03) and developed retinal detachment more frequently (p = 0.08). CONCLUSIONS: Quantitative DNA copy number of ≥5.0 × 106/mL is associated with more extensive retinitis, worse visual acuity, and development of retinal detachment in patients with acute retinal necrosis.

Reduction of Diabetic Macular Edema in the Untreated Fellow Eye Following Intravitreal Injection of Aflibercept.

A 59-year-old patient with bilateral worsening diabetic macular edema received intravitreal injection of aflibercept (Eylea; Regeneron, Tarrytown, NY) to the left eye only. On 1-month follow-up, there was noted bilateral improvement of visual acuity and diabetic macular edema on spectral-domain optical coherence tomography imaging, reflecting bilateral effect of unilateral treatment with aflibercept. [Ophthalmic Surg Lasers Imaging Retina. 2016;47:474-476.].

Linear interstitial keratitis: a distinct clinical entity revisited.

PURPOSE: Few reports in the ophthalmic literature describe rare corneal lesions of the stroma that present in a horizontal linear fashion. Although some differences exist among the small number of reported cases, we believe that all these cases represent a distinct clinical entity appropriately titled linear interstitial keratitis. In an attempt to expand the knowledge of this condition of unknown etiology, we present 3 cases of linear interstitial keratitis. METHODS: Case series (3 cases are presented) and literature review. RESULTS: All 3 patients (aged 21-22 years) presented with horizontal linear stromal infiltrates. One patient presented with a corneal perforation, requiring a closure with 3 interrupted sutures. Another patient required a penetrating keratoplasty because of a visually significant central scar. All 3 patients responded to topical steroids. CONCLUSIONS: Linear interstitial keratitis is a rare clinical entity and its histopathologic etiology remains undetermined. Current available technology including specular microscopy, anterior segment optical coherence tomography, and more sensitive serological testing may permit a better understanding of this disease.

Comparison of Hanna and Hessburg-Barron trephine and punch systems using histological, anterior segment optical coherence tomography, and elliptical curve fitting models.

BACKGROUND: This study analyzes the characteristics of donor and recipient tissue preparation between the Hessburg-Barron and Hanna punch and trephine systems by using elliptical curve fitting models, light microscopy, and anterior segment optical coherence tomography (AS-OCT). METHODS: Eight millimeter Hessburg-Barron and Hanna vacuum trephines and punches were used on six cadaver globes and six corneal-scleral rims, respectively. Eccentricity data were generated using measurements from photographs of the corneal buttons and were used to generate an elliptical curve fit to calculate properties of the corneal button. The trephination angle and punch angle were measured by digital protractor software from light microscopy and AS-OCT images to evaluate the consistency with which each device cuts the cornea. RESULTS: The Hanna trephine showed a trend towards producing a more circular recipient button than the Barron trephine (ratio of major axis to minor axis), ie, 1.059 ± 0.041 versus 1.110 ± 0.027 (P = 0.147) and the Hanna punch showed a trend towards producing a more circular donor cut than the Barron punch, ie, 1.021 ± 0.022 versus 1.046 ± 0.039 (P = 0.445). The Hanna trephine was demonstrated to have a more consistent trephination angle than the Barron trephine when assessing light microscopy images, ie, ±14.39° (95% confidence interval [CI] 111.9-157.7) versus ±19.38° (95% CI 101.9-150.2, P = 0.492) and OCT images, ie, ±8.08° (95% CI 106.2-123.3) versus ±11.16° (95% CI 109.3-132.6, P = 0.306). The angle created by the Hanna punch had less variability than the Barron punch from both the light microscopy, ie, ±4.81° (95% CI 101.6-113.9) versus ±11.28° (95% CI 84.5-120.6, P = 0.295) and AS-OCT imaging, ie, ±9.96° (95% CI 95.7-116.4) versus ±14.02° (95% CI 91.8-123.7, P = 0.825). Statistical significance was not achieved. CONCLUSION: The Hanna trephine and punch may be more accurate and consistent in cutting corneal buttons than the Hessburg-Barron trephine and punch when evaluated using elliptical curve fitting models, light microscopy, and AS-OCT.