Agarwal A, Agrawal R, Raje D, Testi I, Mahajan S, Gunasekeran DV, Aggarwal K, Murthy SI, Westcott M, Chee S-P, McCluskey P, Ho SL, Teoh S, Cimino L, Biswas J, Narain S, Agarwal M, Mahendradas P, Khairallah M, Jones N, Tugal-Tutkun I, Babu K, Basu S, Carreño E, Lee R, Al-Dhibi H, Bodaghi B, Invernizzi A, Goldstein DA, Herbort CP, Barisani-Asenbauer T, González-López JJ, Androudi S, Bansal R, Moharana B, Esposti SD, Tasiopoulou A, Nadarajah S, Agarwal M, Abraham S, Vala R, Singh R, Sharma A, Sharma K, Zierhut M, Kon OM, Cunningham ET, Kempen JH, Nguyen QD, Pavesio C, Gupta V. Twenty-four Month Outcomes in the Collaborative Ocular Tuberculosis Study (COTS)-1: Defining the "Cure" in Ocular Tuberculosis. Ocul Immunol Inflamm 2020;:1-9.Abstract
PURPOSE: To report the clinical findings, anatomical features, and treatment outcomes in subjects with ocular tuberculosis (OTB) at 24 months in the Collaborative Ocular Tuberculosis Study (COTS)-1. METHODS: Of the 945 subjects included in COTS-1, those who completed a 24-month follow-up after completion of treatment were included. The main outcome measure was a number of patients with treatment failure (TF). RESULTS: 228 subjects (120 males; mean age of 42.82 ± 14.73 years) were included. Most common phenotype of uveitis was posterior ( = 81; 35.53%), and panuveitis ( = 76; 33.33%). Fifty-two patients (22.81%) had TF. On univariable analysis, odds of high TF was observed with bilaterality (OR: 3.46, = .003), vitreous haze (OR: 2.14, = .018), and use of immunosuppressive therapies (OR: 5.45, = .003). However, only bilaterality was significant in the multiple regression model (OR: 2.84; = .02). CONCLUSIONS: Majority of subjects (>75%) achieved cure in the COTS-1 at 24-month follow-up. The concept of "cure" may be a valuable clinical endpoint in trials for OTB.
PURPOSE: To evaluate corneal immune dendritiform cell (DC) changes in dry eye disease (DED) using in vivo confocal microscopy (IVCM) and to correlate IVCM parameters with clinical severity. METHODS: This was a retrospective, cross-sectional study including 300 eyes of 150 DED patients and 49 eyes of 49 age-matched controls. Severity of DED was based on the Dry Eye Workshop (DEWS) classification. IVCM images of subbasal layer of the central cornea were analyzed for DC density and morphology (including number of dendrites per DC, DC size and DC field). RESULTS: DC density was significantly higher in DED compared to controls (93.4 ± 6.3 vs. 25.9 ± 3.9 cells/mm; P < 0.001). Morphologically, number of dendrites, DC size and field were significantly larger in DED (3.3 ± 0.1, 106.9 ± 4.7 μm, 403.8 ± 20.1 μm than controls (2.3 ± 0.1, 62.5 ± 5.7 μm, 241.4 ± 24.4 μm, P < 0.001). Significantly higher DC density compared to controls was observed as early as Level 1 DED severity (87 ± 10 cells/mm, p < 0.001. Significant morphological changes in DC were detected for Levels 2 to 4 (p=<0.001, and p =< 0.05) for dendrites and DC field, respectively. Similarly, DC size showed significant increase at DED level 3-4. (p < 0.05). Linear regression analysis showed that both conjunctival and corneal staining were independently associated with DC density, while corneal staining was independently associated with DC morphology. CONCLUSION: DC density and morphology correlated with clinical severity of DED. While, DC density is increased in mild DED, morphological changes are seen only in severe cases. IVCM may be a powerful tool to detect early immune changes and may complement clinical examination in DED.
BACKGROUND: Immunomodulatory therapy (IMT) is often considered for systemic treatment of non-infectious uveitis (NIU). During the evolving coronavirus disease-2019 (COVID-19) pandemic, given the concerns related to IMT and the increased risk of infections, an urgent need for guidance on the management of IMT in patients with uveitis has emerged. METHODS: A cross-sectional survey of international uveitis experts was conducted. An expert steering committee identified clinical questions on the use of IMT in patients with NIU during the COVID-19 pandemic. Using an interactive online questionnaire, guided by background experience and knowledge, 139 global uveitis experts generated consensus statements for IMT. In total, 216 statements were developed around when to initiate, continue, decrease and stop systemic and local corticosteroids, conventional immunosuppressive agents and biologics in patients with NIU. Thirty-one additional questions were added, related to general recommendations, including the use of non-steroidal anti-inflammatory drugs (NSAIDs) and hydroxychloroquine. RESULTS: Highest consensus was achieved for not initiating IMT in patients who have suspected or confirmed COVID-19, and for using local over systemic corticosteroid therapy in patients who are at high-risk and very high-risk for severe or fatal COVID-19. While there was a consensus in starting or initiating NSAIDs for the treatment of scleritis in healthy patients, there was no consensus in starting hydroxychloroquine in any risk groups. CONCLUSION: Consensus guidelines were proposed based on global expert opinion and practical experience to bridge the gap between clinical needs and the absence of medical evidence, to guide the treatment of patients with NIU during the COVID-19 pandemic.
Agrawal R MD FCRS, MBBS GDV, MS AA, MD TI, MD CE, FRCOphth WM, MBBS MS, PhD RD, MS AK, DNB MSI, FRCSEd CSP, MD MP, FRCSGlasg HSL, FRCSEd TS, MD CL, MS BJ, MD NS, MS AM, DNB MP, MD KM, FRCSOphth JN, MD T-TI, DNB BK, MS BS, PhD LR, MD A-DH, MD BB, MD IA, MD GDA, MD HCP, PhD B-AT, PhD G-LJJ, MD AS, MS BR, MS MB, MD ESD, MD TA, MD NS, DNB AM, MD AS, MD VR, MS SR, MD SA, PhD SK, PhD ZM, MRCP KOM, PhD CET, PhD KJH, PhD NQD, FRCSOphth PC, MS GV. Visual Morbidity in Ocular Tuberculosis - Collaborative Ocular Tuberculosis Study (COTS)-1: Report #6. Ocul Immunol Inflamm 2020;:1-9.
Methicillin-resistant (MRSA) is a common cause of severe and difficult to treat ocular infection. In this study, the population structure of 68 ocular MRSA isolates collected at Massachusetts Eye and Ear between January 2014 and June 2016 was assessed. By using a combination of multilocus sequence typing (MLST) analysis, SCC typing and detection of the panton-valentine leukocidin (PVL) gene, we found that the population structure of ocular MRSA is composed of lineages with community and hospital origins. As determined by eBURST analysis of MLST data, the ocular MRSA population consisted of 14 different sequence types (STs) that grouped within two predominant clonal complexes: CC8 (47.0%) and CC5 (41.2%). Most CC8 strains were ST8, harbored type IV SCC and were positive for the PVL-toxin (93.7%). The CC5 group was divided between strains carrying SCC type II (71.4%) and SCC type IV (28.6%). Remaining isolates grouped in 6 different clonal complexes with 3 isolates in CC6 and the other clonal complexes being represented by a single isolate. Interestingly, major MRSA CC5 and CC8 lineages were isolated from discrete ocular niches. Orbital and preseptal abscess/cellulitis were predominantly caused by CC8-SCC IV PVL-positive strains. In contrast, infections of the cornea, conjunctiva and lacrimal system were associated with the MDR CC5 lineage, particularly as causes of severe infectious keratitis. This niche specialization of MRSA is consistent with a model where CC8-SCC IV PVL-positive strains are better adapted to cause infections of the keratinized and soft adnexal eye tissues, whereas MDR CC5 appear to have greater ability in overcoming innate defense mechanisms of the wet epithelium of the ocular surface.
PURPOSE: To investigate whether anti-vascular endothelial growth factor (anti-VEGF) for diabetic macular edema or proliferative diabetic retinopathy (PDR) increases the risk of traction retinal detachment (TRD) among eyes with PDR. METHODS: Pooled analysis of PDR eyes from Protocols I, J, N, S, or T with Early Treatment Diabetic Retinopathy Study level ≥61 (prompt vitrectomy was not planned) randomly assigned to the control group (laser photocoagulation, sham, or intravitreal saline; 396 eyes) or anti-VEGF (487 eyes). The primary outcome was investigator-identified TRD within 1 year of randomization. RESULTS: The 1-year cumulative probability of TRD was 6.8% (95% confidence interval: 4.6%-9.9%, 25 events) in control-group eyes and 4.8% (95% confidence interval: 3.2%-7.3%, 22 events) in anti-VEGF group eyes (hazard ratio = 0.95 [95% confidence interval: 0.54-1.66, P = 0.86]). The cumulative probability of vitrectomy for TRD was 4.4% (16 events) in control-group eyes and 2.2% (9 events) in anti-VEGF group eyes (P = 0.19). Percentage with TRD and vitrectomy for TRD were similar within strata of diabetic retinopathy severity. CONCLUSION: These findings do not support the hypothesis that anti-VEGF therapy for diabetic macular edema or PDR increases the risk of TRD among eyes with PDR similar to those enrolled in five DRCR Retina Network protocols for which prompt vitrectomy was not planned.
A healthy 56-year-old man presented with vision changes and left upper extremity motor and sensory changes. MRI of the brain without contrast was significant for multifocal areas of restricted diffusion in multiple vascular territories. Neuro-Ophthalmic evaluation revealed an inferonasal visual field defect in the left eye, thickened choroid on optical coherence tomography, and bilateral delayed arteriovenous and choroidal filling on fluorescein angiogram. Repeat MRI demonstrated interval enlargement of many of the same foci of abnormal diffusion-weighted imaging signal. Computed tomography of the abdomen and pelvis revealed 3 distinct lobulated retroperitoneal masses that were biopsied and found to be consistent with diffuse large B-cell lymphoma. Brain biopsy specimens showed intravascular lymphocytes, confirming a diagnosis of intravascular lymphoma (IVL). In this diagnostically challenging case, a link was established between the presence of multiple strokes (some of which showed slow evolution over time) and retinochoroidal hypoperfusion, which provided a critical clue to the ultimate diagnosis of IVL.
Cogné B, Latypova X, Senaratne LDS, Martin L, Koboldt DC, Kellaris G, Fievet L, Le Meur G, Caldari D, Debray D, Nizon M, Frengen E, Bowne SJ, Consortium L99, Cadena EL, Daiger SP, Bujakowska KM, Pierce EA, Gorin M, Katsanis N, Bézieau S, Petersen-Jones SM, Occelli LM, Lyons LA, Legeai-Mallet L, Sullivan LS, Davis EE, Isidor B. Mutations in the Kinesin-2 Motor KIF3B Cause an Autosomal-Dominant Ciliopathy. Am J Hum Genet 2020;106(6):893-904.Abstract
Kinesin-2 enables ciliary assembly and maintenance as an anterograde intraflagellar transport (IFT) motor. Molecular motor activity is driven by a heterotrimeric complex comprised of KIF3A and KIF3B or KIF3C plus one non-motor subunit, KIFAP3. Using exome sequencing, we identified heterozygous KIF3B variants in two unrelated families with hallmark ciliopathy phenotypes. In the first family, the proband presents with hepatic fibrosis, retinitis pigmentosa, and postaxial polydactyly; he harbors a de novo c.748G>C (p.Glu250Gln) variant affecting the kinesin motor domain encoded by KIF3B. The second family is a six-generation pedigree affected predominantly by retinitis pigmentosa. Affected individuals carry a heterozygous c.1568T>C (p.Leu523Pro) KIF3B variant segregating in an autosomal-dominant pattern. We observed a significant increase in primary cilia length in vitro in the context of either of the two mutations while variant KIF3B proteins retained stability indistinguishable from wild type. Furthermore, we tested the effects of KIF3B mutant mRNA expression in the developing zebrafish retina. In the presence of either missense variant, rhodopsin was sequestered to the photoreceptor rod inner segment layer with a concomitant increase in photoreceptor cilia length. Notably, impaired rhodopsin trafficking is also characteristic of recessive KIF3B models as exemplified by an early-onset, autosomal-recessive, progressive retinal degeneration in Bengal cats; we identified a c.1000G>A (p.Ala334Thr) KIF3B variant by genome-wide association study and whole-genome sequencing. Together, our genetic, cell-based, and in vivo modeling data delineate an autosomal-dominant syndromic retinal ciliopathy in humans and suggest that multiple KIF3B pathomechanisms can impair kinesin-driven ciliary transport in the photoreceptor.
Intraocular injury by epinephrine auto-injector has been rarely reported. Toxic risk to the intraocular structures is suspected, but the evidence is inconclusive. We present the case of a 2-year-old girl who sustained an injury to her right eye by inadvertent epinephrine injection. Cataract surgery was performed to treat an increasingly opaque lens, and an intraocular lens was implanted. The visual outcome was good, with no retinal damage.
PURPOSE: There have been few systematic reports of vision-related activity limitations of people with retinitis pigmentosa (RP). We report a merging of data from the National Eye Institute Visual Function Questionnaire (NEI-VFQ) obtained in five previous studies. We asked whether the Vision Function Scale (VFS; Pesudovs et al., 2010) which was developed for cataract patients would apply in this new population (condition). METHODS: Five hundred ninety-four individuals completed a total of 1753 questionnaires, with 209 participants providing responses over at least 4 years. Rasch analysis showed that the 15-item VFS was poorly targeted. A new instrument created by adding four driving-related items to the VFS had better targeting. As an indirect validation, VFS-plus person scores were compared to visual field area measured using a Goldmann perimeter, to the summed score for the combined 30-2 and 30/60-1 Humphrey Field Analyzer programs (HFA), to 30-Hz full-field cone electroretinogram (ERG) amplitude, and to ETDRS visual acuity. Changes in VFS-plus person scores with age and between four common heredity groups were also examined. RESULTS: The Rasch model of responses to the 19 VFS-plus items had person and item separation of 2.66 and 24.43 respectively. The VFS-plus person scores were related to each vision measure (p < 0.001). Over a five-year period, there was a reduction in person scores of 0.5 logits (p < 0.001). Person scores fell by an average of 0.34 logits per decade (p < 0.0001). Participants with an X-linked hereditary pattern had, on average, lower person scores (p < 0.001). CONCLUSIONS: The VFS-plus instrument quantified a highly-significant annual reduction in perceived vision-related ability over a five-year period. The outcome was consistent with clinical measures of vision, and detected lower perceived vision-related ability in participants with X-linked disease. It may be of use in future studies, but this needs to be tested in a representative population sample.
AIMS: To compare widefield swept-source optical coherence tomography angiography (WF SS-OCTA) with ultra-widefield colour fundus photography (UWF CFP) and fluorescein angiography (UWF FA) for detecting diabetic retinopathy (DR) lesions. METHODS: This prospective, observational study was conducted at Massachusetts Eye and Ear from December 2018 to October 2019. Proliferative DR, non-proliferative DR and diabetic patients with no DR were included. All patients were imaged with a WF SS-OCTA using a Montage 15×15 mm scan. UWF CFP and UWF FA were taken by a 200°, single capture retinal imaging system. Images were independently evaluated for the presence or absence of DR lesions including microaneurysms (MAs), intraretinal microvascular abnormalities (IRMAs), neovascularisation elsewhere (NVE), neovascularisation of the optic disc (NVD) and non-perfusion areas (NPAs). All statistical analyses were performed using SPSS V.25.0. RESULTS: One hundred and fifty-two eyes of 101 participants were included in the study. When compared with UWF CFP, WF SS-OCTA was found to be superior in detecting IRMAs (p<0.001) and NVE/NVD (p=0.007). The detection rates of MAs, IRMAs, NVE/NVD and NPAs in WF SS-OCTA were comparable with UWF FA images (p>0.05). Furthermore, when we compared WF SS-OCTA plus UWF CFP with UWF FA, the detection rates of MAs, IRMAs, NVE/NVD and NPAs were identical (p>0.005). Agreement (κ=0.916) between OCTA and FA in classifying DR was excellent. CONCLUSION: WF SS-OCTA is useful for identification of DR lesions. WF SS-OCTA plus UWF CFP may offer a less invasive alternative to FA for DR diagnosis.
Minority and low-income patients disproportionately experience dermatologic access challenges. Store-and-forward (SAF) teledermatology has emerged as a model of care delivery that may improve access. We sought to evaluate patterns of utilization and overall impact after SAF teledermatology implementation in a safety-net health care system. We performed a retrospective review of 3,285 teledermatology consultations from 2014 to 2017 in an urban academic safety-net health care system. A total of 1,680 (51.2%) patients were referred for inflammatory/rash conditions and 967 (29.5%) for skin lesions. The teledermatologist recommended in-person evaluation in 1,199 encounters (36.5%). Median wait time for a subsequent appointment was 36 days (range 0-244 days). Of subsequent in-clinic visits, 237 patients (26.4%) underwent skin biopsy. No-show rate after referral was 11.8%. In comparison, median wait time for dermatology appointment through standard referral was 64 days, with a no-show rate of 18.6%. Biopsy rate of patients referred via teledermatology was 26.4%, in comparison to a rate of 10.9% of patients referred directly from primary care provider. Implementation of SAF teledermatology in a safety-net health system resulted in avoidance of 63.5% potential dermatology visits. Consultation typically resulted in a change in suspected diagnosis or management plan. Rates of concordance between teledermatology consults and in-person evaluations were high. Median wait time was reduced by almost half, no-show rate was reduced ∼37%, and biopsy rate was more than double for teledermatology patients compared with standard referral. These findings suggest that SAF teledermatology may improve access to high-quality dermatologic care and increase clinic efficiencies for patients in safety-net health care systems.
The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China in the city of Wuhan in December of 2019 and since then more than 5,000,000 people have been infected, with approximately 338,000 deaths worldwide. The virus causes the coronavirus disease 2019 (COVID-19), which is characterized by fever, myalgia and cough, with severe acute respiratory syndrome being the most fearsome complication. Nevertheless, the vast majority of cases present mild symptoms or none. Central nervous system and cardiovascular manifestations have been reported. The range of ocular manifestations, either as a result of the infection or as a result of the treatment, has not yet been discussed. In this study, a systematic review of current literature relevant to COVID-19 was performed with focus on modes of transmission, ocular manifestations related to infection and medications, as well as the control of infection in ophthalmic practice.
PURPOSE: Angle surgery is the gold standard for the management of many types of childhood glaucoma, yet glaucoma drainage devices (GDD) are effective tools for refractory advanced cases or secondary childhood glaucomas. The purpose of this article is to review recently published literature focused on the use of GDDs for pediatric glaucoma, including GDD general principles and surgical outcomes. METHODS: Literature review of various electronic databases was performed. RESULTS: 71 papers were reviewed for outcomes of GDD in childhood glaucomas. Success rates were usually defined by intraocular pressure (IOP) of 5-22 mmHg, with or without medications. Success rates were typically higher for non-valved GDDs but varied by length of follow-up. Non-valved GDDs afford lower and longer-lasting IOP control in pediatric eyes than valved GDD, however, no randomized controlled trials exist in childhood glaucoma. CONCLUSION: Various designs of GDDs are available for management of childhood glaucoma with good short-term success rates; individual patient factors should be taken into consideration when selecting a specific device.
Erickson S, Sullivan AG, Barabino S, Begovic E, Benitez-Del-Castillo JM, Bonini S, Borges JS, Brzheskiy V, Bulat N, Cerim A, Craig P, Cușnir V, Cușnir V, Cușnir V, Doan S, Dülger E, Farrant S, Geerling G, Goldblum D, Golubev S, Gomes JAP, González-Méijome JM, Grupcheva CN, Gündüz UÖmür, Horwath-Winter J, Källmark F, Karanadze N, Karcic HH, Karcic S, Kontadakis G, Messmer EM, Mrugacz M, Murphy C, O'Leary OE, Procopciuc V, Pult H, Raus P, Şahin A, Setälä N, Stanila A, Stanila DM, Utheim TP, Vehof J, Versura P, Villani E, Willcox MDP, Wolffsohn JS, Zagórski Z, Zoega GMár, Sullivan DA, Sullivan DA, Gomes JAP, Versura P, Willcox MDP. TFOS European ambassador meeting: Unmet needs and future scientific and clinical solutions for ocular surface diseases. Ocul Surf 2020;Abstract
The mission of the Tear Film & Ocular Surface Society (TFOS) is to advance the research, literacy, and educational aspects of the scientific field of the tear film and ocular surface. Fundamental to fulfilling this mission is the TFOS Global Ambassador program. TFOS Ambassadors are dynamic and proactive experts, who help promote TFOS initiatives, such as presenting the conclusions and recommendations of the recent TFOS DEWS II™, throughout the world. They also identify unmet needs, and propose future clinical and scientific solutions, for management of ocular surface diseases in their countries. This meeting report addresses such needs and solutions for 25 European countries, as detailed in the TFOS European Ambassador meeting in Rome, Italy, in September 2019.
PURPOSE: To report long term results of treatment with intravitreal injections of aflibercept in a newly diagnosed case of Coats' disease. CASE REPORT: An 18-year-old man presented to the Retina Clinic of our Hospital complaining of blurred vision in the right eye (OD) for the past 3 months. His past medical and ocular history were unremarkable. Best corrected visual acuity (BCVA) was 20/200 OD and 20/20 in the left eye. Fundoscopy in OD revealed extensive macular edema with a circinate ring of hard exudates in the posterior pole temporally to the macula. Optical coherence tomography (OCT) demonstrated macular edema with subretinal fluid. Peripheral telangiectasias and light bulb aneurysms in the inferior temporal arcade, as well as in the nasal far periphery were found in OD in fluorescein angiography (FA), confirming the diagnosis of stage 2B Coats' disease. The left eye was normal. The original therapeutic strategy proposed was anti-VEGF injections in OD followed by laser photocoagulation. However, the patient did not consent to laser treatment and was treated with aflibercept monotherapy with 8 monthly intravitreal injections of aflibercept followed by 6 injections every 2 months for a total of 14 injections over a period of 2 years. The BCVA in OD improved to 20/25 while OCT imaging revealed significant decrease in retinal thickness with resolution of macular edema and FA demonstrated prominent regression of aneurysms and leakage. CONCLUSION: To our knowledge this is the first case treated with aflibercept monotherapy, suggesting the significant role of vascular endothelial growth factor (VEGF) in vascular permeability in Coats' and supporting the rationale that anti-VEGFs are a valuable therapeutic option for Coats' disease.