Purpose:Vision-degrading myodesopsia (VDM) from vitreous floaters significantly degrades vision and impacts visual quality of life (VQOL), but the relationship to light scattering is poorly understood. This study compared in vitro measures of light scatter and transmission in surgically excised human vitreous to preoperative indexes of vitreous structure, visual function, and VQOL. Methods:Pure vitreous collected during vitrectomy from 8 patients with VDM had wide-angle straylight measurements and dark-field imaging, performed within 36 hours of vitrectomy. Preoperative VQOL assessment with VFQ-25, contrast sensitivity (CS) measurements with Freiburg acuity contrast testing, and quantitative ultrasonography were compared to light scattering and transmission in vitro. Results:All indices of vitreous echodensity in vivo correlated positively with straylight at 0.5° (R = 0.708 to 0.775, P = 0.049 and 0.024, respectively). Straylight mean scatter index correlated with echodensity (R = 0.71, P = 0.04) and VQOL (R = -0.82, P = 0.0075). Dark-field measures in vitro correlated with degraded CS in vivo (R = -0.69, P = 0.04). VQOL correlated with straylight mean scatter index (R = -0.823, P = 0.012). Conclusions:Increased vitreous echodensity in vivo is associated with more straylight scattering in vitro, validating ultrasonography as a clinical surrogate for light scattering. Contrast sensitivity in vivo is more degraded in the presence of dark-field scattering in vitro and VQOL is decreased in patients whose vitreous has increased light scattering. These findings could form the basis for the development of optical corrections for VDM or support new laser treatments, as well as novel pharmacotherapy.

PURPOSE:Limited vitrectomy improves vision degrading myodesopsia, but the incidence of recurrent floaters postoperatively is not known. We studied patients with recurrent central floaters using ultrasonography and contrast sensitivity (CS) testing to characterize this subgroup and identify the clinical profile of patients at risk of recurrent floaters.METHODS:A total of 286 eyes (203 patients, 60.6 ± 12.9 years) undergoing limited vitrectomy for vision degrading myodesopsia were studied retrospectively. Sutureless 25G vitrectomy was performed without intentional surgical posterior vitreous detachment (PVD) induction. CS (Freiburg Acuity Contrast test: Weber index, %W) and vitreous echodensity (quantitative ultrasonography) were assessed prospectively.RESULTS:No eyes (0/179) with preoperative PVD experienced new floaters. Recurrent central floaters occurred in 14/99 eyes (14.1%) without complete preoperative PVD (mean follow-up = 39 months vs. 31 months in 85 eyes without recurrent floaters). Ultrasonography identified new-onset PVD in all 14 (100%) recurrent cases. Young (younger than 52 years; 71.4%), myopic (≥-3D; 85.7%), phakic (100%) men (92.9%) predominated. Reoperation was elected by 11 patients, who had partial PVD preoperatively in 5/11 (45.5%). At study entry, CS was degraded (3.55 ± 1.79 %W) but improved postoperatively by 45.6% (1.93 ± 0.86 %W, P = 0.033), while vitreous echodensity reduced by 86.6% ( P = 0.016). New-onset PVD postoperatively degraded CS anew, by 49.4% (3.28 ± 0.96 %W; P = 0.009) in patients electing reoperation. Repeat vitrectomy normalized CS to 2.00 ± 0.74%W ( P = 0.018).CONCLUSION:Recurrent floaters after limited vitrectomy for vision degrading myodesopsia are caused by new-onset PVD, with younger age, male sex, myopia, and phakic status as risk factors. Inducing surgical PVD at the primary operation should be considered in these select patients to mitigate recurrent floaters.

A 76-year-old female with hearing loss and microhematuria without renal dysfunction presented with bilateral macular retinoschisis related to autosomal recessive Alport syndrome, representing the first case of macular retinoschisis in autosomal recessive disease.

Introduction Hyalocytes are sentinel macrophages residing within the posterior vitreous cortex anterior to the retinal inner limiting membrane (ILM). Following anomalous PVD and vitreoschisis, hyalocytes contribute to paucicellular (vitreo-macular traction syndrome, macular holes) and hypercellular (macular pucker, proliferative vitreo-retinopathy, proliferative diabetic vitreo-retinopathy) diseases.Areas covered Studies of human tissues employing dark-field, phase, and electron microscopies; immunohistochemistry; and in vivo imaging of human hyalocytes.Expert opinion Hyalocytes are important in early pathophysiology, stimulating cell migration and proliferation, as well as subsequent membrane contraction and vitreo-retinal traction. Targeting hyalocytes early could mitigate advanced disease. Ultimately, eliminating the role of vitreous and hyalocytes may prevent proliferative vitreo-retinal diseases entirely.

Purpose: To define injection index (II) and assess its impact on visual acuity (VA) in pigment epithelial detachment from age-related macular degeneration over 5 years. Methods: Injection index is defined as the mean anti–vascular endothelial growth factor injections per year from presentation. A retrospective study of 256 eyes in 213 patients was performed. Patients were stratified by II (high: ≥9, low: <9). Results: Baseline characteristics showed no differences across II groups. Mean (range) follow-up, in years, was 5.02 (1.04–12.74) for all patients. Mean logMAR VA (Snellen VA) were 0.60 (20/80) and 0.56 (20/73) at baseline, 0.52 (20/66) and 0.59 (20/78) at Year 1, 0.45 (20/56) and 0.67 (20/94) at Year 2, 0.38 (20/48) and 0.66 (20/91) at Year 3, 0.41 (20/51) and 0.89 (20/155) at Year 4, and 0.35 (20/45) and 0.79 (20/123) at Year 5 for the high and low II groups, respectively. Linear regression analysis showed a gain of 0.5 approxETDRS letters with each additional injection per year. Conclusion: Increased II was associated with better mean VA, suggesting that long-term continuous vascular endothelial growth factor suppression may improve VA in eyes thought to carry poor prognoses.

BACKGROUND:To describe the clinical presentation and characteristic imaging features of deep retinal haemorrhages primarily located in the Henle fibre layer (HFL) of the macula. The spectrum of aetiologies and a comprehensive theory of pathogenesis are presented.METHODS:This is a retrospective, multicentre case series evaluating eyes with retinal haemorrhage in HFL. Clinical features, underlying aetiology, systemic and ocular risk factors, visual acuity, and multimodal imaging including fundus photography and cross-sectional and en face optical coherence tomography (OCT) are presented.RESULTS:Retinal haemorrhages localised to HFL in 33 eyes from 23 patients were secondary to acute blunt trauma to the head (n=2), eye (n=1) and trunk (n=1), ruptured intracranial aneurysm (Terson's syndrome, n=3), general anaesthesia (n=1), epidural anaesthesia (n=1), hypertension with anaemia (n=1), decompression retinopathy (n=1), postvitrectomy with intraocular gas (n=1), retinal vein occlusion (n=7), myopic degeneration (n=2), macular telangiectasia type 2 (n=1), and polypoidal choroidal vasculopathy (n=1). Defining clinical features included deep retinal haemorrhage with feathery margin and petaloid pattern radiating from the fovea. OCT demonstrated characteristic hyper-reflectivity from the haemorrhage delineated by obliquely oriented fibres in the Henle layer. Spontaneous resolution of HFL haemorrhage occurred after 3 months in 15 patients with follow-up.CONCLUSION:The characteristic petaloid-shaped, deep intraretinal haemorrhage with a feathery margin localised to HFL is associated with various disorders. The terminology 'Henle fiber layer hemorrhage (HH)' is proposed to describe the clinical and OCT findings, which may result from abnormal retinal venous pressure from systemic or local retinovascular disorders affecting the deep capillary plexus or from choroidal vascular abnormalities.

Purpose: To define injection index (II) and assess its impact on visual acuity (VA) in pigment epithelial detachment from age-related macular degeneration over 5 years. Methods: Injection index is defined as the mean anti-vascular endothelial growth factor injections per year from presentation. A retrospective study of 256 eyes in 213 patients was performed. Patients were stratified by II (high: >= 9, low: <9). Results: Baseline characteristics showed no differences across II groups. Mean (range) follow-up, in years, was 5.02 (1.04-12.74) for all patients. Mean logMAR VA (Snellen VA) were 0.60 (20/80) and 0.56 (20/73) at baseline, 0.52 (20/66) and 0.59 (20/78) at Year 1, 0.45 (20/56) and 0.67 (20/94) at Year 2, 0.38 (20/48) and 0.66 (20/91) at Year 3, 0.41 (20/51) and 0.89 (20/155) at Year 4, and 0.35 (20/45) and 0.79 (20/123) at Year 5 for the high and low II groups, respectively. Linear regression analysis showed a gain of 0.5 approxETDRS letters with each additional injection per year. Conclusion: Increased II was associated with better mean VA, suggesting that long-term continuous vascular endothelial growth factor suppression may improve VA in eyes thought to carry poor prognoses.

Hydrocinnamoyl-L-valylpyrrolidine (AS-1), a synthetic low-molecule mimetic of myeloid differentiation primary response gene 88 (MyD88), inhibits inflammation by disrupting the interaction between the interleukin-1 receptor (IL-1R) and MyD88. Here, we describe the effects of AS-1 on injury-induced increases in inflammation and neovascularization in mouse corneas. Mice were administered a subconjunctival injection of 8 μL AS-1 diluent before or after corneal alkali burn, followed by evaluation of corneal resurfacing and corneal neovascularization (CNV) by slit-lamp biomicroscopy and clinical assessment. Corneal inflammation was assessed by whole-mount CD45+ immunofluorescence staining, and corneal hemangiogenesis and lymphangiogenesis following injury were evaluated by immunostaining for the vascular markers isolectin B4 (IB4) and the lymphatic vascularized marker lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), respectively. Additionally, corneal tissues were collected to determine the expression of 35 cytokines, and we detected activation of IL-1RI, MyD88, and mitogen-activated protein kinase (MAPK). The results showed that alkali conditions increased the number of CD45+ cells and expression of vascular endothelial growth factor (VEGF)-A, VEGF-C, and LYVE1 in corneas, with these levels decreased in the AS-1-treated group. Moreover, AS-1 effectively prevented alkali-induced cytokine production, blocked interactions between IL-1RI and MyD88, and inhibited MAPK activation post-alkali burn. These results indicated that AS-1 prevented alkali-induced corneal hemangiogenesis and lymphangiogenesis by blocking IL-1RI–MyD88 interaction, as well as extracellular signal-regulated kinase phosphorylation, and could be efficacious for the prevention and treatment of corneal alkali burn.

PURPOSE:To assess the feasibility of imaging extremely low birth weight infants, defined as infants born weighing less than 1000 g or before 27 weeks of gestational age, with an arm-mounted optical coherence tomography angiography (OCTA) device. METHODS:Cross-sectional case series conducted at a single site in-patient academic center. Subjects included infants who had been born premature and met ROP screening criteria. Birth history such as gestational age and birth weight were collected. Subjects were imaged with OCTA in a supine position during ROP screening and treatment. Segmental errors were manually corrected and FAZ area was calculated from the superficial and deep capillary plexus (SCP, DCP) layers. Main outcomes measures were foveal avascular zone (FAZ) area, ROP stage and treatment. RESULTS:Seven ELBW infants were included with an average gestational age of 25 weeks (range = 23-4/7 to 26 weeks) and average postmenstrual age of 54.7 weeks (range = 43-80 weeks) at the time of imaging. Average birth weight was 615 g (range 500-680 grams). Thirteen eyes had ROP treatment including primary laser, anti-vascular endothelial growth factor injection with delayed laser, and scleral buckle. Six infants were imaged under general anesthesia and one infant was imaged without sedation. Average FAZ area was 0.17 mm2 (range = 0.03 mm2-0.37 mm2) in the SCP and 0.04 mm2 (range 0 mm2-0.09 mm2) in the DCP. FAZ area correlated positively to the ratio of outer retinal layer thickness to inner retinal layer thickness at the foveal center in the SCP and DCP (r2 = 0.48, p = 0.02; r2 = 0.46, p = 0.02) and negatively with inner retinal layer thickness in the SCP (r2 = 0.56, p = 0.008). CONCLUSIONS AND IMPORTANCE:Arm-mounted OCTA was feasible in ELBW infants and provided information about the developing fovea. Measurement of FAZ area and retinal thickness using this modality may be used to study the effects of ELBW, peripheral ROP and ROP treatment on foveal development.

Purpose: Acanthamoeba keratitis (AK) is a severe vision-threatening ocular infection that is frequently a diagnostic challenge. Treatment course is lengthy and often not fully effective. Contact lens wear has been recognized as the prime risk factor for AK. In vivo confocal microscopy (IVCM) is a noninvasive imaging modality that allows direct visualization of potential causative pathogens in real time with an established utility in the diagnosis of AK. In this study, we aim to assess the utility of IVCM in monitoring disease progression in contact lens wearers with culture-confirmed keratitis. Methods: Fourteen eyes from 11 patients with culture-confirmed AK were included in this retrospective study. IVCM was performed during the patient's initial visit and all follow-up visits. All available confocal sequences were reviewed and graded in a masked fashion. Density of Acanthamoeba cyst infiltration and changes in the cyst density as a percentage of baseline cyst density measured at each patient's initial visit were calculated. A univariate regression analysis was performed to assess the association between treatment and changes in cyst density per month of treatment. Results: Acanthamoeba cysts were identified by IVCM in all of these culture-confirmed cases of keratitis. Mean cyst density in the central cornea at presentation was 99 ± 64.9 cells per square millimeter (range, 38–255/mm2). Cyst density in our study population significantly decreased by approximately 5.3% with each month of antiamebic treatment (P = 0.001; R2 = 0.41). Conclusions: Reduction in Acanthamoeba cyst density with treatment can be monitored by IVCM, which in turn can be used clinically in prognostication and disease monitoring of AK.

PURPOSE:To investigate the utility of in vivo confocal microscopy (IVCM) in the diagnosis of infectious keratitis (IK).METHODS:Retrospective chart review of 46 patients with a final diagnosis of IK were included in the study. All patients received IVCM corneal imaging using the Heidelberg Retinal Tomography III system. All available scans were randomized and analyzed in a masked fashion. Sensitivity and specificity of IVCM in diagnosing bacterial keratitis (BK), Acanthamoeba keratitis (AK), fungal keratitis (FK), and HSV viral keratitis (VK) were assessed.RESULTS:The pooled sensitivity and specificity of IVCM in identifying atypical IK (AK and FK cases combined) were 85.3% (95% CI 68.2-94.5%) and 100% (95% CI 74.7-100%), respectively. The sensitivity and specificity of IVCM in identifying BK were 66.7% (95% CI 35.4-88.7%) and 89.2% (95% CI 73.4-96.5%), respectively. The sensitivity and specificity of IVCM in identifying VK were 100% (95% CI 46.3-100%) and 93.2% (95% CI 80.3-98.2%). Additionally, IVCM was able to make the correct diagnosis in 8 out of the 11 atypical keratitis cases misdiagnosed clinically. In the AK subgroup, IVCM was more accurate than clinical assessment (16 vs. 11). In the FK subgroup, IVCM were as accurate as clinical assessment, but did correct one misdiagnosed cases by identfying fungal hyphae.CONCLUSION:IVCM is an non-invasive imaging modality that can rapidly and accurately diagnose IK even for experienced corneal specialists. In complex cases of polymicrobial infection, IVCM may guide the correct clinical diagnosis and initiation of the appropriate treatment.

Purpose: To report a genotype-phenotype correlation study of patients with retinitis pigmentosa (RP) based on ultra-widefield (UWF) fundus autofluorescence (FAF) imaging. Design: Case series. Participants: Thirty-four patients with RP. Methods: This retrospective study included RP patients with confirmed causative genetic variants and UWF FAF imaging data. Qualitative grading criteria including the pattern of macular abnormal autofluorescence, decreased autofluorescence (DAF), and its extent and distribution were applied to evaluate the genotype-phenotype correlation. Main Outcome Measures: The main parameters measured were increased or decreased patterns and extent of autofluorescence. Results: Thirty-four unrelated patients 38 +/- 19 years of age (range, 9-82 years) were enrolled. Mutations in 17 different genes were detected in patients, including 7 patients having mutations in USH2A, 4 in DHDDS, 4 in RPGR, 3 in PRPF31, and 3 in RP1. Patients with nummular DAF and widespread DAF were significantly older (59 +/- 14 years and 56 +/- 19 years, respectively). All 3 patients with PRPF31 mutations showed an abnormal macular ring hyperautofluorescence and a circular pattern of coarse DAF distributed in Early Treatment Diabetic Retinopathy Study fields 1, 2, and 3 with sparing of the far periphery. In other genotypes, no specific DAF or macular abnormal autofluorescence pattern could be discerned. Conclusions: Specific UWF FAF characteristics in RP patients were correlated strongly with patient age and stage of the disease. Particular UWF FAF characteristics were found to be more prominent in a unique genotype. (C) 2017 by the American Academy of Ophthalmology

PURPOSE:To report a case of bilateral central retinal artery occlusion with both anterior and posterior ischemic optic neuropathy.OBSERVATIONS:A 65-year-old Caucasian woman presented with acute respiratory distress syndrome and septic shock. After treatment with vasopressors and prolonged prone positioning, she was noted to be bilaterally completely blind on hospitalization day 12. Evaluation revealed evidence of bilateral central retinal artery occlusion and bilateral ischemic optic neuropathy. Magnetic resonance imaging of the orbits demonstrated severe restricted diffusion of both optic nerves consistent with ischemia. Both central retinal artery occlusion and ischemic optic neuropathy have been reported in cases of severe hypotension, blood loss, and prone positioning, most often postoperatively after spinal surgery.CONCLUSIONS AND IMPORTANCE:To our knowledge, this is the first reported case of bilateral central retinal artery occlusion with both anterior and posterior ischemic optic neuropathy, presumed due to the combination of severe systemic hypotension, hypoxemia due to the respiratory distress syndrome, and prolonged prone positioning.

Purpose: To report the first case of a cone dystrophy with central ellipsoid zone loss associated with a mutation in the human retinal fascin gene (FSCN2). Methods: Multimodal retinal imaging findings including spectral domain optical coherence tomography and fundus autofluorescence are presented. The results of functional testing and mutational analysis are also discussed. Patients: Single patient with a diagnosis of cone dystrophy. Results: Spectral domain optical coherence tomography imaging illustrated central loss of the ellipsoid zone band in each eye. Full-field and multifocal electroretinogram testing confirmed a diagnosis of cone dystrophy in a 35-year-old male patient. Subsequent cone dystrophy genetic panel identified a novel mutation (p.Pro406Leu:c.1217C>T) in the FSCN2 gene. Conclusion: This is the first case report of a patient diagnosed with cone dystrophy associated with a novel mutation in the FSCN2 gene. FSCN2 genetic testing should be considered in patients with central ellipsoid loss and cone dystrophy, especially as specific gene therapy treatments emerge in the future.

BACKGROUND:Isocyanates are one of the most commonly reported causes of occupational asthma; however, the risks of developing isocyanate asthma in modern production facilities remain poorly defined. We evaluated TDI exposure and respiratory health among an inception cohort of workers during their first year of employment at a new polyurethane foam production factory.METHODS:Forty-nine newly hired workers were evaluated pre-employment, 6-months, and 12-months post-employment through questionnaire, spirometry, and TDI-specific serology. Airborne TDI levels were monitored by fixed-point air sampling and limited personal sampling. Qualitative surface SWYPE™ tests were performed to evaluate potential sources of skin exposure.RESULTS:Airborne TDI levels overall were low; over 90% of fixed-point air measurements were below the limit of detection (0.1 ppb). Over the first year of employment, 12 of the 49 original workers (24.5%) were lost to follow-up, no additional workers were enrolled, and seven of the 49 original workers (14.2%) developed either new asthma symptoms (N = 3), TDI-specific IgG (N = 1), new airflow obstruction (N = 1) and/or a decline in FEV1  ≥ 15% (N = 3), findings that could indicate TDI-related health effects. The prevalence of current asthma symptoms was significantly higher in the workers lost to follow-up compared to those who completed the 12-month follow-up (25% vs. 2.7%; P = 0.04).CONCLUSIONS:The findings suggest possible early TDI-related health effects in a modern polyurethane production plant. These findings also highlight the need for further longitudinal evaluation of these workers and the challenges of studying workers at risk for isocyanate asthma.

Vision I It seemed like a typical Monday morning. I was a fourth-year medical student on my year-long immersion in ophthalmology. At morning report, the first-year residents spoke assuredly about the patients seen over the weekend, giving the impression that all was business as usual. Another corneal abrasion here. Another ruptured globe there. Afterwards, I walked to the waiting area and saw someone sitting there who looked quite familiar. What was she doing here? Should I examine her? After all, she was the dean, beloved by medical students. Eventually, I asked, “Is it okay for me to take an initial history and exam?” “Yes, of course,” she replied. Gathering the history was daunting. As she vividly recalled her symptoms, I attempted to ignore my distracting thoughts. Are my questions open-ended enough? Am I making appropriate eye-contact? I could sense she was worried, and I tried to provide what answers I could. The thought of laying hands on her eyelids made me feel uneasy, but I carried on. First, a test of vision. Check. Next, pupils and intraocular pressure. Check and check. Still, I secretly hoped that the slit lamp’s luminous beam would conceal my heightened self-consciousness. In medical school, I’d been taught the essentials of treating all patients with equal dignity and respect. However, when my dean was the one sitting in the patient chair, I fought the urge to display exceptional empathy, respect, and understanding; it no longer felt like business as usual. I think it is easy to be seduced by the familiar rhythms of daily practice, but it is also easy to forget sometimes that every patient–provider encounter leaves an indelible mark on both the patient’s and the provider’s fabric of life. For that reason, patient care should never be business as usual. I aspire to practice medicine with an established standard of care while always paying attention to the uniqueness of each individual, each dean and each patient alike. Vision II Roles are reversed in the blink of an eye. Literally in my case, as I found myself sitting on the other side of a slit lamp from a fourth-year medical student, one of my medical students as I am the dean of students at his medical school. In the waiting area, I sat worrying about my left eye. Two days earlier I had seen a brief flash of light, and the following day a large, dark floater obscured my vision. I ruminated on the worst outcome—permanent vision loss. A smiling and familiar face appeared. Seeing someone I knew in this terrifying situation was comforting. He took me into a room where he dilated my eyes, tested my vision, measured intraocular pressures, and was present both for my diagnosis of retinal tear and for the laser treatment that followed. He was calm, reassuring, always sitting at eye level, explaining what he could and assuring me that his preceptor would explain more. This experience brought to mind a vivid scene from years ago when I visited a former residency director in the hospital after her treatment for breast cancer. The door to her room was ajar, and I saw her leaning forward engrossed in the words of her oncologist, who had been a resident with me in her program. We practically pounce on first-year medical students to impress upon them the importance of professionalism. We want them to grow up in front of our eyes and understand their new role as physician-to-be. They often come to us wearing their flip-flops and backward baseball caps. We hope that by steeping them in pathophysiology, applying white jackets, and engaging them with patient-centered care, they will become the professionals we would want for ourselves or our family members. In our hearts, we know the journey from premed to professional is a process with fits and starts that takes time. Performance on objective structured clinical examinations is a surrogate marker for the knowledge, skills, and attitudes that we hope they will accumulate and practice, but we may never know for sure. One day, however, we will walk into a room feeling vulnerable, needy, and scared, and see a student or former student or a colleague’s former student in front of us. At that moment, we must believe in the process and put ourselves in his hands. Wei Gui and Nancy R. Angoff, MD, MPH, MEd Mr. Gui is a fourth-year medical student, Yale University School of Medicine, New Haven, Connecticut; e-mail: [email protected] Dr. Angoff is associate dean for student affairs and associate professor of medicine, Yale University School of Medicine, New Haven, Connecticut; e-mail: [email protected]

PURPOSE:To compare vision-related (VR-QOL) and health-related quality of life (HR-QOL) in patients with noninfectious uveitis treated with systemic anti-inflammatory therapy versus nonsystemic therapy.METHODS:A prospective, cross-sectional study design was employed. VR-QOL and HR-QOL were assessed by the 25-Item Visual Function Questionnaire (VFQ-25) and the Short Form 12-Item Health Survey (SF-12), respectively. Multivariate regression analysis was performed to assess the VR-QOL and HR-QOL based on treatment.RESULTS:Among the 80 patients, the median age was 51 years with 28 males (35%). The adjusted effect of treatment modality on VR-QOL or HR-QOL showed no statistically significant difference in all subscores of VFQ-25 or physical component score (PCS) and mental component score (MCS) of SF-12. Systemic therapy did not compromise VR-QOL or HR-QOL compared to nonsystemic therapy.CONCLUSIONS:Systemic therapy can be effectively used to control serious cases of noninfectious uveitis without significant relative adverse impact on quality of life.