TUBERCULOUS CHORIORETINITIS: A CHALLENGING CASE OF AN OPHTHALMIC MIMIC.

PURPOSE: To report a challenging case of tuberculous chorioretinitis. METHODS: Case report of a 51-year-old woman from the Middle East, who was referred from an optometrist with a suspicious retinal lesion in her right eye. RESULTS: Clinical examination showed multifocal, pale, elevated lesions temporal to the right macula with no vasculitis or hemorrhages. Infective and inflammatory workup showed unremarkable results. B-scan ultrasound confirmed an 8 mm × 3 mm × 10 mm right focal chorioretinal thickening. Computed tomography scanning showed calcified lung hilar nodes supporting a prior granulomatous process, along with an enhancing nodule in the right globe. Magnetic resonance imaging of the brain and obits showed retinal thickening of the temporal surface of the right globe with subtle enhancement without retrobulbar extension or evidence for cerebral vasculitis. Subretinal lesion biopsy showed mononuclear inflammatory cells with granulomatous inflammation, including multinucleated giant cells but no neoplastic features. Interferon-gamma release assay testing for tuberculosis showed negative result, but a high index of suspicion lead to tuberculin skin testing and subsequent treatment for tuberculous chorioretinitis. CONCLUSION: Ocular tuberculosis presents in a variety of ways, making it a challenging diagnosis. Herein, we describe such case of tuberculous chorioretinitis.

Fundus fluorescein angiography imaging of retinopathy of prematurity in infants: A review.

Fluorescein angiography in retinopathy of prematurity is increasingly utilized over the past decade. The development of ultra-wide-field imaging combined with fluorescein angiography has allowed improved visualization of the peripheral retinal vasculature. Patient cooperation in the pediatric population is particularly challenging, but hand-held digital retinal photography has shown promise and can visualize the infant retina without the need for anesthesia and intravenous access. Many features of retinopathy of prematurity and its response to laser and anti-VEGF treatment can be either exclusively or better visualized on fluorescein angiography compared to indirect ophthalmoscopy or color fundus photography. Disease treatment is gradually shifting from laser photocoagulation to intravitreal anti-VEGF agents, the latter being associated with late-onset vision-threatening sequelae. The role of fluorescein angiography in retinopathy of prematurity monitoring will continue to increase with the longer follow-up required and different clinical behavior seen with anti-VEGF treatment. We highlight the utility, safety, and importance of fluorescein angiography in the diagnosis, treatment, and follow-up of retinopathy of prematurity.

Controlling a Digital Cursor With a Sterile Gyroscopic Mouse in Digitally Assisted Vitreoretinal Surgery.

PURPOSE: To describe our experience using the gyroscopic mouse in digitally assisted vitreoretinal surgery. METHODS: We used a commercially available gyroscopic mouse to control the on-screen cursor of the NGENUITY System for digitally assisted vitreoretinal surgery. The gyroscopic mouse is sealed in a clear sterile plastic bag to allow for intraoperative use. This allowed both the surgeon and assistant to be fully scrubbed while retaining full control of the NGENUITY system's functions. The mouse also allowed the mentor to provide detailed instructions through the on-screen cursor by highlighting important landmarks. CONCLUSION: Using a sterile gyroscopic mouse improved the teaching utility and surgical workflow of digitally assisted vitreoretinal surgery.

Suprachoroidal Gas: A Rare Complication of Intravitreal Injection of Perfluoropropane.

This is a case report of a 75-year-old pseudophakic male, who presented with a massive submacular hemorrhage on a background of neovascular age-related macular degeneration. Intravitreal perfluoropropane was used to attempt pneumatic displacement of the submacular hemorrhage. The next day, subconjunctival gas was observed, with no gas seen in the vitreous cavity. Fundal examination showed suprachoroidal detachment. CT images confirmed gas entrapment, with no choroidal hemorrhage identified. The following case report describes suprachoroidal gas as a complication of intravitreal injection of perfluoropropane for pneumatic displacement of submacular hemorrhage. To our knowledge, this is the first such case in the literature. We describe the approach in differentiating suprachoroidal gas from hemorrhage and comment on a plausible mechanism for this complication. This report also serves as a review of the current state of knowledge in the area of suprachoroidal gas as a complication of pneumatic retinopexy and sutureless vitrectomy.

Multimodal Retinal Imaging and Microperimetry Reveal a Novel Phenotype and Potential Trial End Points in CRB1-Associated Retinopathies.

Purpose: Biallelic crumbs cell polarity complex component 1 (CRB1) mutations can present as Leber congenital amaurosis (LCA), retinitis pigmentosa (RP), or cystic maculopathy. This study reports a novel phenotype of asymptomatic fenestrated slit maculopathy (AFSM) and examines macular volume profile and microperimetry as clinical trial end points in CRB1-associated retinopathies. Methods: Twelve patients from nine families with CRB1 mutation were recruited. Ultra-widefield (UWF) color fundus photography and autofluorescence (AF), spectral-domain optical coherence tomography (SD-OCT), microperimetry, and adaptive optics (AO) imaging were performed. Macular volume profiles were compared with age-matched healthy controls. Genotyping was performed using APEX genotyping microarrays, targeted next-generation sequencing, and Sanger sequencing. Results: We identified one patient with LCA, five patients with RP, and four patients with macular dystrophy (MD) with biallelic CRB1 mutations. Two siblings with compound heterozygote genotype (c.[2843G>A]; [498_506del]) had AFSM characterized by localized outer retinal disruption on SD-OCT and parafoveal cone loss on AO imaging despite normal fundus appearance, visual acuity, and foveal sensitivity. UWF AF demonstrated preserved para-arteriolar retinal pigment epithelium (PPRPE) in all patients with RP. Microperimetry documented preserved central retinal function in six patients. The ratio of perifoveal-to-foveal retinal volume was greater than controls in 89% (8/9) of patients with RP or MD, whereas central subfield and total macular volume were outside normal limits in 67% (6/9). Conclusions: AO imaging was helpful in detecting parafoveal cone loss in asymptomatic patients. Macular volume profile and microperimetry parameters may have utility as CRB1 trials end points. Translational Relevance: Macular volume and sensitivity can be used as structural and functional end points for trials on CRB1-associated RP and MD.

Anti-VEGF crunch syndrome in proliferative diabetic retinopathy: A review.

Anti-vascular endothelial growth factor (anti-VEGF) crunch syndrome describes the progression to tractional retinal detachment following intravitreal anti-VEGF therapy in an eye with proliferative diabetic retinopathy . We reviewed the literature on the anti-VEGF crunch using the PubMed and Cochrane databases. Anti-VEGF crunch typically manifests as sudden vision loss in the affected eye between 1 and 6 weeks following intravitreal anti-VEGF injection, with a mean onset of 13 days. Risk factors for crunch development include the use of a higher anti-VEGF dose and increased severity of diabetic retinopathy with fibrosis. Our review found that intravitreal anti-VEGF, in particular bevacizumab, should be used with caution when treating patients with severe proliferative diabetic retinopathy and pre-existing intraocular fibrosis. In patients where anti-VEGF is used before a planned vitrectomy, we recommend close monitoring for crunch symptoms and proceeding promptly with surgery if there is new or progression of tractional retinal detachment. For eyes with minimal preexisting traction that develop crunch after anti-VEGF treatment, surgeons should proceed to vitrectomy within 7 days. The existing literature on the anti-VEGF crunch is limited by heterogeneity in the way crunch is documented and characterized and the presence of panretinal photocoagulation as a confounding factor. Because of these methodological flaws, the relative frequency of the anti-VEGF crunch cannot be accurately estimated.

Prospective Longitudinal Evaluation of Nascent Geographic Atrophy in Age-Related Macular Degeneration.

PURPOSE: Nascent geographic atrophy (nGA) describes features on OCT imaging previously observed to precede the development of atrophy. This study sought to prospectively evaluate the predictive ability of nGA for the conventional clinical endpoint of geographic atrophy (GA) as defined on color fundus photography (CFP). DESIGN: Prospective, longitudinal, observational study. PARTICIPANTS: A total of 284 eyes from 142 participants with bilateral large drusen and without nGA nor late age-related macular degeneration (AMD) at baseline were included. METHODS: OCT volume scans and CFP images were obtained from all participants at baseline and then at 6-month intervals for up to 36 months. OCT and CFP images were graded independently for the presence of nGA and GA, respectively. Eyes that developed neovascular AMD were censored at the day of its detection. MAIN OUTCOME MEASURES: Time to development of GA. RESULTS: A total 12 eyes from 10 participants progressed to GA over 36 months of follow-up, and nGA was detected in 10 of these eyes (83%) at a preceding visit (median, 13 months prior; interquartile range, 6-25 months). A total of 40 eyes from 28 participants developed nGA or GA over 36 months of follow-up, and the probability of progression to nGA and GA after 36 months was 20% (95% confidence interval [CI], 14%-28%) and 9% (95% CI, 6%-13%), respectively. After the detection of nGA, the probability of progression to GA was 38% (95% CI, 15%-55%) after 24 months. The development of nGA was associated with a markedly increased risk of progression to GA compared with when it did not develop (adjusted hazard ratio, 78.1; 95% CI, 13.6-448.0; P < 0.001), and the development of nGA explained 91% of the variance in the time to GA development. CONCLUSIONS: This study prospectively demonstrated that nGA was a strong predictor for the development of GA, providing supportive evidence of the potential value of nGA as a surrogate endpoint in future intervention trials for the early stages of AMD to improve their feasibility substantially.

Secondary and Exploratory Outcomes of the Subthreshold Nanosecond Laser Intervention Randomized Trial in Age-Related Macular Degeneration: A LEAD Study Report.

PURPOSE: To evaluate the secondary and exploratory outcomes of the Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study, a 36-month trial of a subthreshold nanosecond laser (SNL) treatment for slowing the progression to late age-related macular degeneration (AMD) in its early stages. DESIGN: Multicenter, randomized, sham-controlled trial. PARTICIPANTS: Two-hundred ninety-two patients with bilateral large drusen. METHODS: Participants were randomly assigned to receive SNL or sham treatment to the study eye at 6-month intervals. MAIN OUTCOME MEASURES: The secondary outcome measure of the LEAD study was the time to development of late AMD, defined by multimodal imaging in the non-study eye. The exploratory outcome measures were the rate of change in best-corrected visual acuity (BCVA), low-luminance visual acuity, microperimetric mean sensitivity, drusen volume in the study and non-study eyes, and participant-reported outcomes based on the Night Vision Questionnaire and Impact of Vision Impairment questionnaire. RESULTS: Progression to late AMD in the non-study eye was not significantly delayed with SNL treatment (hazard ratio, 0.83; 95% confidence interval, 0.40-1.71; P = 0.611). There was no evidence of effect modification based on the coexistence of reticular pseudodrusen; interaction P = 0.065). There was no significant difference between study groups in the rate of change of low-luminance visual acuity, microperimetric mean sensitivity, and drusen volume in the study or non-study eyes, and Night Vision Questionnaire and Impact of Vision Impairment questionnaire scores (all P ≥ 0.167). The rate of BCVA decline was slightly higher for participants in the SNL group compared with the sham treatment group in the study eye (-0.54 and 0.23 letters/year, respectively; P < 0.001) but not the non-study eye (-0.48 and -0.56 letters/year, respectively; P = 0.628). CONCLUSIONS: Subthreshold nanosecond laser treatment of one eye did not have an effect on delaying progression to late AMD in the fellow eye and did not, in general, have an impact on the exploratory structural, functional, and participant-reported outcomes.

Subthreshold Nanosecond Laser Intervention in Age-Related Macular Degeneration: The LEAD Randomized Controlled Clinical Trial.

PURPOSE: There is an urgent need for a more effective intervention to slow or prevent progression of age-related macular degeneration (AMD) from its early stages to vision-threatening late complications. Subthreshold nanosecond laser (SNL) treatment has shown promise in preclinical studies and a pilot study in intermediate AMD (iAMD) as a potential treatment. We aimed to evaluate the safety of SNL treatment in iAMD and its efficacy for slowing progression to late AMD. DESIGN: The Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study is a 36-month, multicenter, randomized, sham-controlled trial. PARTICIPANTS: Two hundred ninety-two participants with bilateral large drusen and without OCT signs of atrophy. METHODS: Participants were assigned randomly to receive Retinal Rejuvenation Therapy (2RT®; Ellex Pty Ltd, Adelaide, Australia) SNL or sham treatment to the study eye at 6-monthly intervals. MAIN OUTCOME MEASURES: The primary efficacy outcome was the time to development of late AMD defined by multimodal imaging (MMI). Safety was assessed by adverse events. RESULTS: Overall, progression to late AMD was not slowed significantly with SNL treatment compared with sham treatment (adjusted hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.33-1.14; P = 0.122). However, a post hoc analysis showed evidence of effect modification based on the coexistence of reticular pseudodrusen (RPD; adjusted interaction P = 0.002), where progression was slowed for the 222 participants (76.0%) without coexistent RPD at baseline (adjusted HR, 0.23; 95% CI, 0.09-0.59; P = 0.002), whereas an increased progression rate (adjusted HR, 2.56; 95% CI, 0.80-8.18; P = 0.112) was observed for the 70 participants (24.0%) with RPD with SNL treatment. Differences between the groups in serious adverse events were not significant. CONCLUSIONS: In participants with iAMD without MMI-detected signs of late AMD, no significant difference in the overall progression rate to late AMD between those receiving SNL and sham treatment were observed. However, SNL treatment may have a role in slowing progression for those without coexistent RPD and may be inappropriate in those with RPD, warranting caution when considering treatment in clinical phenotypes with RPD. Our findings provide compelling evidence for further trials of the 2RT® laser, but they should not be extrapolated to other short-pulse lasers.

Subthreshold Nanosecond Laser Intervention in Intermediate Age-Related Macular Degeneration: Study Design and Baseline Characteristics of the Laser in Early Stages of Age-Related Macular Degeneration Study (Report Number 1).

PURPOSE: The Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study is an investigation of the safety and efficacy of subthreshold nanosecond laser treatment to slow the progression of intermediate age-related macular degeneration (AMD). This report presents the novel study design and baseline characteristics. DESIGN: Multicenter, double-masked, randomized controlled, medical device feasibility clinical trial. PARTICIPANTS: Persons with bilateral drusen >125 µm within 1500 µm of the fovea, monocular best-corrected visual acuity (BCVA) ≥20/40, and microperimetric retinal sensitivity of <25 decibels (dB) in at least 1 location within central 6° in 1 eye. Signs of late AMD; choroidal neovascularization or geographic atrophy, or anatomic end points defined on multimodal imaging (MMI) as fundus autofluorescence-defined atrophy, spectral-domain OCT (SD-OCT)-defined atrophy, or nascent GA excluded participation. METHODS: Participants were randomized to nanosecond or sham laser treatment. Twelve laser or sham spots are applied to the macular region of the study eye. Participants are reviewed in visits every 6 months with functional testing and MMI for 36 months and are re-treated at each visit (until 30 months) if an end point is not reached in the study eye. MAIN OUTCOME MEASURES: Progression to late AMD or MMI-defined anatomic end points in the study eye. RESULTS: A total of 292 participants across 6 centers were enrolled, with 145 participants randomized to arm 1 and 147 participants randomized to arm 2. Population characteristics at baseline were as follows: median age 70 years, 73% female, 90% Anglo-Saxon, and 3% current smokers. Baseline ocular characteristics of the study eyes were BCVA of 83 letters (20/25); low luminance visual acuity (LLVA) of 68 letters (20/50); hyperpigmentation, 33%; reticular pseudodrusen, 23%; square root drusen area (SD-OCT), 0.77 mm; square root drusen area (color photographs), 0.92 mm; cube root drusen volume (SD-OCT), 0.26 mm; average retinal sensitivity, 26 dB; and worst point retinal sensitivity, 20 dB. Only lutein supplement use was significantly different between treatment arms. CONCLUSIONS: The LEAD study uses novel inclusion/exclusion criteria and end points in an attempt to optimize our study design. Risk characteristics for progression to study end points are equally distributed between treatment arms.

Aqueous Chlorhexidine for Intravitreal Injection Antisepsis: A Case Series and Review of the Literature.

PURPOSE: To determine the incidence of endophthalmitis in a large clinical series using aqueous chlorhexidine for antisepsis before intravitreal injection and to review the ophthalmic literature regarding chlorhexidine efficacy and safety. DESIGN: Multicenter retrospective case series. PARTICIPANTS: All patients receiving intravitreal injections from 7 retinal specialists. METHODS: An audit of intravitreal injections performed by retinal specialists who exclusively used aqueous chlorhexidine 0.05% or 0.1% for prophylaxis of infective endophthalmitis was undertaken. The incidence of endophthalmitis was determined from August 1, 2011, to February 28, 2015. A literature review was performed to critically appraise the ocular safety and efficacy of aqueous chlorhexidine. MAIN OUTCOME MEASURES: Incidence of endophthalmitis after intravitreal injections. RESULTS: A total of 40 535 intravitreal injections were performed by 7 retinal specialists across 3 centers. Chlorhexidine was well tolerated, and only 1 patient with a suspected allergic reaction was noted. Three cases of endophthalmitis were identified with 1 culture-positive case. The 0.0074% (1 in 13 512) per-injection rate of endophthalmitis in this series compares favorably with previous series in which povidone-iodine has been used. CONCLUSIONS: Aqueous chlorhexidine was associated with a low rate of postinjection endophthalmitis and was well tolerated by patients.

Antemortem vitreous potassium may strengthen postmortem interval estimates.

The purpose of this letter is to highlight that postmortem interval estimates using vitreous potassium concentrations may be further optimised by calibration against antemortem vitreous samples.