Importance: Optic neuritis (ON) in children is uncommon. There are limited prospective data for visual acuity (VA) outcomes, associated diseases, and neuroimaging findings. Prospective data from a large sample would be useful for counseling families on treatment decisions and prognosis. Objective: To prospectively study children with a first episode of ON, describe VA after 6 months, and ascertain the network's (Pediatric Eye Disease Investigator Group and Neuro-Ophthalmology Research Disease Investigator Consortium) ability to enroll pediatric patients with ON prospectively. Design, Setting, and Participants: This nonrandomized cohort study was conducted from September 20, 2016, to July 20, 2018, at 23 sites in the United States and Canada in pediatric ophthalmology or neuro-ophthalmology clinics. A total of 44 children (aged 3-15 years) presented with a first episode of ON (visual loss, pain on eye movements, or both) within 2 weeks of symptom onset and at least 1 of the following in the affected eye: a distance high-contrast VA (HCVA) deficit of at least 0.2 logMAR below age-based norms, diminished color vision, abnormal visual field, or optic disc swelling. Exclusion criteria included preexisting ocular abnormalities or a previous episode of ON. Main Outcomes and Measures: Primary outcomes were monocular HCVA and low-contrast VA at 6 months. Secondary outcomes were neuroimaging, associated diagnoses, and antibodies for neuromyelitis optica and myelin oligodendrocyte glycoprotein. Results: A total of 44 children (mean age [SD], 10.2 [3.5] years; 26 boys [59%]; 23 White individuals [52%]; 54 eyes) were enrolled in the study. Sixteen patients (36%) had bilateral ON. Magnetic resonance imaging revealed white matter lesions in 23 children (52%). Of these children, 8 had myelin oligodendrocyte glycoprotein-associated demyelination (18%), 7 had acute disseminated encephalomyelitis (16%), 5 had multiple sclerosis (11%), and 3 had neuromyelitis optica (7%). The baseline mean HCVA was 0.95 logMAR (20/200), which improved by a mean 0.76 logMAR (95% CI, 0.54-0.99; range, -0.70 to 1.80) to 0.12 logMAR (20/25) at 6 months. The baseline mean distance low-contrast VA was 1.49 logMAR (20/640) and improved by a mean 0.72 logMAR (95% CI, 0.54-0.89; range, -0.20 to 1.50) to 0.73 logMAR (20/100) at 6 months. Baseline HCVA was worse in younger participants (aged <10 years) with associated neurologic autoimmune diagnoses, white matter lesions, and in those of non-White race and non-Hispanic ethnicity. The data did not suggest a statistically significant association between baseline factors and improvement in HCVA. Conclusions and Relevance: The study network did not reach its targeted enrollment of 100 pediatric patients with ON over 2 years. This indicates that future treatment trials may need to use different inclusion criteria or plan a longer enrollment period to account for the rarity of the disease. Despite poor VA at presentation, most children had marked improvement by 6 months. Associated neurologic autoimmune diagnoses were common. These findings can be used to counsel families about the disease.

BACKGROUNDHyperglycemia, insulin insensitivity, and low IGF1 levels in extremely preterm infants are associated with an increased risk of retinopathy of prematurity (ROP), but the interactions are incompletely understood.METHODSIn 117 extremely preterm infants, serum glucose levels and parenteral glucose intake were recoded daily in the first postnatal week. Serum IGF1 levels were measured weekly. Mice with oxygen-induced retinopathy alone versus oxygen-induced retinopathy plus streptozotocin-induced hyperglycemia/hypoinsulinemia were assessed for glucose, insulin, IGF1, IGFBP1, and IGFBP3 in blood and liver. Recombinant human IGF1 was injected to assess the effect on glucose and retinopathy.RESULTSThe highest mean plasma glucose tertile of infants positively correlated with parenteral glucose intake [r(39) = 0.67, P < 0.0001]. IGF1 plasma levels were lower in the high tertile compared with those in low and intermediate tertiles at day 28 (P = 0.038 and P = 0.03). In high versus lower glucose tertiles, ROP was more prevalent (34 of 39 versus 19 of 39) and more severe (ROP stage 3 or higher; 71% versus 32%). In oxygen-induced retinopathy, hyperglycemia/hypoinsulinemia decreased liver IGF1 expression (P < 0.0001); rh-IGF1 treatment improved normal vascular regrowth (P = 0.027) and reduced neovascularization (P < 0.0001).CONCLUSIONIn extremely preterm infants, high early postnatal plasma glucose levels and signs of insulin insensitivity were associated with lower IGF1 levels and increased ROP severity. In a hyperglycemia retinopathy mouse model, decreased insulin signaling suppressed liver IGF1 production, lowered serum IGF1 levels, and increased neovascularization. IGF1 supplementation improved retinal revascularization and decreased pathological neovascularization. The data support IGF1 as a potential treatment for prevention of ROP.TRIAL REGISTRATIONClinicalTrials.gov NCT02760472 (Donna Mega).FUNDINGThis study has been supported by the Swedish Medical Research Council (14940, 4732, 20144-01-3, and 21144-01-3), a Swedish government grant (ALFGB2770), Lund medical faculty grants (ALFL, 11615 and 11601), the Skåne Council Foundation for Research and Development, the Linnéa and Josef Carlsson Foundation, the Knut and Alice Wallenberg Foundation, the NIH/National Eye Institute (EY022275, EY017017, EY017017-13S1, and P01 HD18655), European Commission FP7 project 305485 PREVENT-ROP, Deutsche Forschungsgemeinschaft (CA-1940/1-1), and Stiftelsen De Blindas Vänner.

To develop an automated retina layer thickness measurement tool for the ImageJ platform, to quantitate nuclear layers following the retina contour. We developed the ThicknessTool (TT), an automated thickness measurement plugin for the ImageJ platform. To calibrate TT, we created a calibration dataset of mock binary skeletonized mask images with increasing thickness masks and different rotations. Following, we created a training dataset and performed an agreement analysis of thickness measurements between TT and two masked manual observers. Finally, we tested the performance of TT measurements in a validation dataset of retinal detachment images. In the calibration dataset, there were no differences in layer thickness between measured and known thickness masks, with an overall coefficient of variation of 0.00%. Training dataset measurements of immunofluorescence retina nuclear layers disclosed no significant differences between TT and any observer's average outer nuclear layer (ONL) (p = 0.998), inner nuclear layer (INL) (p = 0.807), and ONL/INL ratio (p = 0.944) measurements. Agreement analysis showed that bias between TT vs. observers' mean was lower than between any observers' mean against each other in the ONL (0.77 ± 0.34 µm vs 3.25 ± 0.33 µm) and INL (1.59 ± 0.28 µm vs 2.82 ± 0.36 µm). Validation dataset showed that TT can detect significant and true ONL thinning (p = 0.006), more sensitive than manual measurement capabilities (p = 0.069). ThicknessTool can measure retina nuclear layers thickness in a fast, accurate, and precise manner with multi-platform capabilities. In addition, the TT can be customized to user preferences and is freely available to download.

OBJECTIVE: To determine the most commonly used and highest-rated mobile applications (apps) for low-vision aids. METHODS: This was a convenience sample survey. Patients known to use low-vision apps at a nonprofit low-vision center (INSIGHT, Warwick, RI) were contacted by phone between June and September 2019. INCLUSION CRITERIA: age 18+, Snellen visual acuity (VA) below 20/70, and the use of low-vision mobile apps for at least one month. A standardized script was used to record survey data and app ratings were evaluated by patients with a scale of one to five, one being the lowest and five being the highest. RESULTS: Of the sample (n=11), nine patients (81.8%) stated they used an iPhone for low-vision mobile apps. A list of 14 mobile apps was identified: the two most commonly used apps were Seeing AI (81.8%) and Be My Eyes (63.6%); their average ratings were 4.43/5 and 4.75/5, respectively. CONCLUSIONS: This survey suggests that Seeing AI and Be My Eyes are useful apps to help low- vision patients with activities of daily living.

PURPOSE: To report the incidence of symptomatic vertical and torsional diplopia after superior rectus transposition (SRT) for esotropic Duane syndrome and abducens nerve palsy. METHODS: The medical records of patients with esotropic Duane syndrome or abducens nerve palsy seen at Boston Children's Hospital (2006-2018) and treated with unilateral SRT with or without augmentation was performed. The primary outcome was incidence of postoperative vertical or torsional diplopia in primary position. The secondary outcome was induced vertical deviation in affected side gaze. RESULTS: A total of 69 patients met inclusion criteria: 32 with abducens nerve palsy and 37 with esotropic Duane syndrome. Vertical alignment changed in both hyper- and hypotropic directions. Median pre- and postoperative vertical deviation in primary gaze was 1.1 (10th-90th percentile, 0-6 hypertropia) and 0.4 (10th-90th percentile, 6 hypotropia to 8 hypertropia), respectively. Postoperative vertical diplopia occurred in 7%, including 4 of 49 treated with loop myopexy (8%), 1 of 13 without augmentation (8%), and 0 of 7 treated with sclera-fixated augmentation. All but one was successfully treated with prism or secondary surgery. Intorsional change predominated, but no patient had torsional diplopia post adjustment. Vertical misalignment in affected side gaze increased from 19% to 45% after SRT (P = 0.01). CONCLUSIONS: In this largest-to-date review of patients treated with SRT, with or without MR recession, no patient developed persistent torsional diplopia, while 7% developed symptomatic vertical diplopia in primary position, similar to the reported incidence after balanced vertical rectus transposition. Vertical misalignment in affected side gaze increased, however fusion is already limited by unresolved esotropia in this field.

Purpose: The purpose of this study was to visualize the lamina cribrosa (LC) capillaries and collagenous beams, measure capillary tortuosity (path length over straight end-to-end length), and determine if capillary tortuosity changes when intraocular pressure (IOP) increases. Methods: Within 8 hours of sacrifice, 3 pig heads were cannulated via the external ophthalmic artery, perfused with PBS to remove blood, and then perfused with a fluorescent dye to label the capillaries. The posterior pole of each eye was mounted in a custom-made inflation chamber for control of IOP with simultaneous imaging. Capillaries and collagen beams were visualized with structured light illumination enhanced imaging at IOPs from 5 to 50 mm Hg at each 5 mm Hg increment. Capillary tortuosity was measured from the images and paired two-sample t-tests were used to assess for significant changes in relation to changes in IOP. Results: Capillaries were highly tortuous at 15 mm Hg (up to 1.45). In all but one eye, tortuosity decreased significantly as IOP increased from 15 to 25 mm Hg (P < 0.01), and tortuosity decreased significantly in every eye as IOP increased from 15 to 40 mm Hg (P < 0.01). In only 16% of capillaries, tortuosity increased with elevated IOP. Capillaries had a surprisingly different topology from the collagen beams. Conclusions: Although high capillary tortuosity is sometimes regarded as potentially problematic because it can reduce blood flow, LC capillary tortuosity may provide slack that mitigates against reduced flow and structural damage caused by excessive stretch under elevated IOP. We speculate that low capillary tortuosity could be a risk factor for damage under high IOP.

Purpose: Although zebrafish rods begin to develop as early as 2 days postfertilization (dpf), they are not deemed anatomically mature and functional until 15 to 21 dpf. A recent study detected a small electroretinogram (ERG) from rods in a cone mutant called no optokinetic response f (nof) at 5 dpf, suggesting that young rods are functional. Whether they can mediate behavioral responses in larvae is unknown. Methods: We first confirmed rod function by measuring nof ERGs under photopic and scotopic illumination at 6 dpf. We evaluated the role of rods in visual behaviors using two different assays: the visual-motor response (VMR) and optokinetic response (OKR). We measured responses from wild-type (WT) larvae and nof mutants under photopic and scotopic illuminations at 6 dpf. Results: Nof mutants lacked a photopic ERG. However, after prolonged dark adaptation, they displayed scotopic ERGs. Compared with WT larvae, the nof mutants displayed reduced VMRs. The VMR difference during light onset gradually diminished with decreased illumination and became nearly identical at lower light intensities. Additionally, light-adapted nof mutants did not display an OKR, whereas dark-adapted nof mutants displayed scotopic OKRs. Conclusions: Because the nof mutants lacked a photopic ERG but displayed scotopic ERGs after dark adaptation, the mutants clearly had functional rods. WT larvae and the nof mutants displayed comparable scotopic light-On VMRs and scotopic OKRs after dark adaptation, suggesting that these responses were driven primarily by rods. Together, these observations indicate that rods contribute to zebrafish visual behaviors as early as 6 dpf.

BACKGROUND: To prevent irreversible vision loss in age-related macular degeneration (AMD), it is critical to detect retinal dysfunction before permanent structural loss occurs. In the current study we evaluated a series of visual function tests to identify potential endpoints to detect visual dysfunction in non-advanced AMD. METHODS: A series of visual function tests were performed on 23 non-advanced AMD subjects (AREDS grade 1-4 on simplified scale) and 34 age-matched normals (AREDS grade 0). Tests included some commonly used endpoints such as ETDRS visual acuity (VA), low luminance (LL) 2.0ND ETDRS VA, MNREAD as well as newly developed tests such as the Ora-VCF™ test, Ora-tablet reading test, color sensitivity etc. Differences between the two groups were compared for each test. Test-retest repeatability and reproducibility was assessed on a subset of subjects and percent agreement was calculated. RESULTS: There was no difference in standard ETDRS VA between non-advanced AMD (0.06 ± 0.02 logMAR) and normal groups (0.04 ± 0.02 logMAR) (p = 0.57). LL 2.0 ETDRS VA and MNREAD showed no difference between the groups (p > 0.05). Ora-VCF™ test was significantly worse in the non-advanced AMD group compared to normals (0.67 ± 0.07 in AMD; 0.45 ± 0.04 in normals, p = 0.005). Non-advanced AMD subjects also had significantly worse reading performance using the Ora-tablet with LL 2.0ND (114.55 ± 11.22 wpm in AMD; 145.17 ± 9.55 wpm in normals p = 0.049). No significant difference between the groups was noted using other tests. Repeatability was 82% for Ora-VCF™ test and 92% for Ora-tablet LL 2.0ND reading. Reproducibility was 89% for both Ora-VCF™ test and Ora-tablet LL 2.0ND reading. CONCLUSION: While there was no significant difference between non-advanced AMD and normal groups using some current common endpoints such as ETDRS VA, LL 2.0 ETDRS VA or MNREAD, Ora-VCF™ test and Ora-tablet LL 2.0ND reading tests were able to identify significant visual dysfunction in non-advanced AMD subjects. These tests show promise as endpoints for AMD studies.

This article was withdrawn on October 15, 2020, at the request of the journal editors, with agreement from the authors, owing to a substantial amount of unattributed or improperly cited text overlap with other sources. In accordance with Annual Reviews' commitment to transparency, the original PDF of the article remains available for download at .

Purpose: To identify factors affecting family members' decision whether to donate eye organs. Methods: A community-based case-control study based on in-home interviews with families of deceased individuals who had or had not donated eye organs, in Madurai district, Tamil Nadu, India. Data collected were knowledge and awareness of eye donations, whether the deceased individual had expressed or pledged willingness to donate, and family members' attitudes and willingness to donate their own eye organs. Results: Seventy-six families of donors and 256 families of non-donors completed the survey. Multivariable analysis showed that the following variables were significantly associated with a donation: age, whether the deceased had registered for eye donation, pre-expressed willingness of deceased to donate, whether family members personally know beneficiaries of eye donations, and higher score on a scale evaluating knowledge and awareness about eye donation. The majority of donors' families (71%) had been encouraged by someone to donate. Among non-donor families, a substantially larger fraction (52.8%) indicated they would have donated had someone reminded or encouraged them to do so, in comparison with those who indicated lack of awareness or knowledge (14.5%). Conclusion: Community programs are likely to be effective if they encourage individuals to pledge their eyes or express their willingness to donate their eyes to family members in advance of death; they increase public awareness of the value of eye donation. A friend, family member, neighbor or counselor approaching bereaved families and having a dialogue about eye donation would substantially increase the probability of a decision to donate.

The neural mechanism of phantom limb pain (PLP) is related to the intense brain reorganization process implicating plasticity after deafferentation mostly in sensorimotor system. There is a limited understanding of the association between the sensorimotor system and PLP. We used a novel task-based functional magnetic resonance imaging (fMRI) approach to (1) assess neural activation within a-priori selected regions-of-interested (motor cortex [M1], somatosensory cortex [S1], and visual cortex [V1]), (2) quantify the cortical representation shift in the affected M1, and (3) correlate these changes with baseline clinical characteristics. In a sample of 18 participants, we found a significantly increased activity in M1 and S1 as well as a shift in motor cortex representation that was not related to PLP intensity. In an exploratory analyses (not corrected for multiple comparisons), they were directly correlated with time since amputation; and there was an association between increased activity in M1 with a lack of itching sensation and V1 activation was negatively correlated with PLP. Longer periods of amputation lead to compensatory changes in sensory-motor areas; and itching seems to be a protective marker for less signal changes. We confirmed that PLP intensity is not associated with signal changes in M1 and S1 but in V1.

Purpose: This article describes the clinical and multimodal imaging characteristics of subthreshold exudative choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD). Methods: Among 3773 patients with AMD, 8 eyes (6 patients) were identified with the clinical phenotype of interest. Dilated fundus examinations, color fundus photography, fluorescein angiography (FA), indocyanine green angiography (ICGA), optical coherence tomography (OCT), and OCT angiography (OCTA) were performed. Results: OCT typically showed a moderately reflective irregular pigment epithelial detachment with overlying subretinal fluid (SRF). Traditional FA did not show leakage and ICGA showed no definitive neovascular network or hot spots. However, OCTA clearly demonstrated a CNV within the pigment epithelial detachment. The majority of our cases (7 of 8) did not receive antivascular endothelial growth factor (anti-VEGF) injections, and visual acuity remained stable over the available follow-up period of I to 10 years. Conclusions: CNV is often associated with SRF and vision loss in AMD, usually requiring frequent anti-VEGF injections. OCTA allowed us to better identify CNV not readily detected on FA and ICGA. Although some have suggested early clinical intervention with anti-VEGF injections in any case with fluid and confirmed CNV on OCTA, we describe a subset of AMD patients with SRF who may be better managed by observation. These cases may represent a more indolent, mature, and stable vascular network.

: to summarize the origin and very recent history of the use of metagenomic sequencing for the diagnosis of infectious uveitis, convey the technique as described by one of the primary institutions experimenting with the technology, and present recent successful applications of the technology as well as potential advantages and pitfalls compared to other current diagnostic tools.: review of peer-reviewed literature concerning metagenomic sequencing for the diagnosis of infectious uveitis.: compared to existing diagnostic methods, metagenomic deep sequencing is a sensitive, unbiased, and comprehensive technique with great potential for diagnosing the causative pathogens of cases of infectious uveitis. However, many issues remain to be addressed in the process of developing this technology, including but not limited to the potentially overwhelming amount of information generated, definition of diagnostic thresholds, demonstration of validity, contamination, and cost.

Amiodarone is an anti-arrhythmic drug that was approved by the US Food and Drug Administration (FDA) in 1985. Pre-clinical studies suggest that Amiodarone induces cytotoxicity in several types of cancer cells, thus making it a potential candidate for use as an anti-cancer treatment. However, it is also known to cause a variety of severe side effects. We hypothesized that in addition to the cytotoxic effects observed in cancer cells Amiodarone also has an indirect effect on angiogensis, a key factor in the tumor microenvironment. In this study, we examined Amiodarone's effects on a murine tumor model comprised of U-87 MG glioblastoma multiforme (GBM) cells, known to form highly vascularized tumors. We performed several in vitro assays using tumor and endothelial cells, along with in vivo assays utilizing three murine models. Low dose Amiodarone markedly reduced the size of GBM xenograft tumors and displayed a strong anti-angiogenic effect, suggesting dual cancer fighting properties. Our findings lay the ground for further research of Amiodarone as a possible clinical agent that, used in safe doses, maintains its dual properties while averting the drug's harmful side effects.

Viral vectors have a great potential for gene delivery, but manufacturing at a pharmaceutical scale is a big challenge for the industry. The baculovirus-insect cell system is one of the most scalable platforms to produce clinical-grade recombinant Adeno-Associated Virus (rAAV) vectors. The standard procedure to generate recombinant baculovirus is based on Tn7 transposition which is time-consuming and still suffers technical constraints. Moreover, werecently showed that baculoviral sequences adjacent to the AAV ITRs are preferentially encapsidated into the rAAV vector particles. This observation raised concerns about safety for clinical applications due to the presence of bacterial and antibiotic resistance coding sequences with a Tn7-mediated system for the construction of baculoviruses reagents. Here, weinvestigated a faster and safer method based on homologous recombination (HR). First, weconfirmed the functionality of the inserted cassette and the absence of undesirable genes into HR-derived baculoviral genomes. Strikingly, wefound that the exogenous cassette showed increased stability over passages when using the HR system. Finally, wetested these materials to produce rAAV vectors. The baculoviruses originated from both systems lead to high rAAV vector genome yields, with the advantage of the HR system being exempted from undesirable bacterial genes which provides an additional level of safety for the manufacturing of rAAV vectors. Overall, this study highlights the importance of the upstream process and starting biologic materials to generate safer rAAV biotherapeutic products. This article is protected by copyright. All rights reserved.

On the occasion of being awarded the Prentice Medal, I was asked to summarize my translational journey. Here I describe the process of becoming a low-vision rehabilitation clinician and researcher, frustrated by the unavailability of effective treatments for some conditions. This led to decades of working to understand patients' needs and the complexities and subtleties of their visual systems and conditions. It was followed by many iterations of developing vision aids and the techniques needed to objectively evaluate their benefit. I specifically address one path: the invention and development of peripheral prisms to expand the visual fields of patients with homonymous hemianopia, leading to our latest multiperiscopic prism (mirror-based design) with its clear 45° field-of-view image shift.

Corneal stiffness plays a critical role in shaping the cornea with respect to intraocular pressure and physical interventions. However, it remains difficult to measure the mechanical properties noninvasively. Here, we report the first measurement of shear modulus in human corneas in vivo using optical coherence elastography (OCE) based on surface elastic waves. In a pilot study of 12 healthy subjects aged between 25 and 67, the Rayleigh-wave speed was 7.86 ± 0.75 m/s, corresponding to a shear modulus of 72 ± 14 kPa. Our data reveal two unexpected trends: no correlation was found between the wave speed and IOP between 13-18 mmHg, and shear modulus decreases with age (- 0.32 ± 0.17 m/s per decade). We propose that shear stiffness is governed by the interfibrillar matrix, whereas tensile strength is dominated by collagen fibrils. Rayleigh-wave OCE may prove useful for clinical diagnosis, refractive surgeries, and treatment monitoring.

We present a retrospective of unique micro-fabrication problems and solutions that were encountered through over 10 years of retinal prosthesis product development, first for the Boston Retinal Implant Project initiated at the Massachusetts Institute of Technology and at Harvard Medical School's teaching hospital, the Massachusetts Eye and Ear-and later at the startup company Bionic Eye Technologies, by some of the same personnel. These efforts culminated in the fabrication and assembly of 256+ channel visual prosthesis devices having flexible multi-electrode arrays that were successfully implanted sub-retinally in mini-pig animal models as part of our pre-clinical testing program. We report on the processing of the flexible multi-layered, planar and penetrating high-density electrode arrays, surgical tools for sub-retinal implantation, and other parts such as coil supports that facilitated the implantation of the peri-ocular device components. We begin with an overview of the implantable portion of our visual prosthesis system design, and describe in detail the micro-fabrication methods for creating the parts of our system that were assembled outside of our hermetically-sealed electronics package. We also note the unique surgical challenges that sub-retinal implantation of our micro-fabricated components presented, and how some of those issues were addressed through design, materials selection, and fabrication approaches.

BACKGROUND: Glaucoma is one of the leading causes of blindness worldwide. Treatment is still largely targeted at lowering intraocular pressure. Intraocular pressures can be lowered through a variety of topical medications, lasers and incisional surgeries. There are currently several classes of topical medications available in the US that are aimed at lowering intraocular pressure through a variety of different mechanisms. Additionally, there have been numerous different formulations and fixed-dose combination medications that offer greatly expanded treatment options over the last several years. The wide variety of topical medications aim to address the issues with compliance, effectiveness and side effect profile that vary among each individual patient and disease.  Purpose: Three new topical medications, netarsudil 0.02%, latanoprostene bunod 0.24% and fixed-dose combination netarsudil 0.02% - latanoprost 0.005% have been approved in the US market to treat glaucoma. This review article will summarize the studies looking at their effectiveness and side effect profiles and discuss their utilization in the treatment of glaucoma. Additionally, we will briefly discuss future directions of research in topical glaucoma medications. CONCLUSION: Three new topical glaucoma medications offer additional treatment options for patient with glaucoma. Further research is needed to better understand the utility of sustained release formulations in the treatment of glaucoma.

Phase unwrapping is one of the major challenges in multiple branches of science that extract three-dimensional information of objects from wrapped signals. In several applications, it is important to extract the unwrapped information with minimal signal resolution degradation. However, most of the denoising techniques for unwrapping are designed to operate on the entire phase map to remove a limited number of phase residues, and therefore they significantly degrade critical information contained in the image. In this paper, we present a novel, smart, and automatic filtering technique for locally minimizing the number of phase residues in noisy wrapped holograms, based on the phasor average filtering (PAF) of patches around each residue point. Both patch sizes and PAF filters are increased in an iterative algorithm to minimize the number of residues and locally restrict the artifacts caused by filtering to the pixels around the residue pixels. Then, the improved wrapped phase can be unwrapped using a simple phase unwrapping technique. The feasibility of our method is confirmed by filtering, unwrapping, and enhancing the quality of a noisy hologram of neurons; the intensity distribution of the spatial frequencies demonstrates a 40-fold improvement, with respect to previous techniques, in preserving the higher frequencies.

PURPOSE: To describe a case of paraneoplastic pemphigus (PNP) presenting as spontaneous bilateral corneal perforations in a patient with follicular dendritic cell sarcoma. METHODS: Retrospective chart review Results: A 73-year-old Greek woman with a history of follicular dendritic cell sarcoma (FDCS) presented with bilateral corneal perforations and a cicatrizing conjunctivitis. Her diagnosis was consistent with PNP with corneal and conjunctival involvement after a change in her chemotherapy regimen from intravenous cyclophosphamide to gemcitabine. She was treated with a multilayered amniotic membrane in the right eye and cyanoacrylate glue in the left eye. Systemic intravenous cyclophosphamide and oral prednisone were re-started. Both perforations healed but the patient passed away soon after precluding further follow-up. CONCLUSIONS: Ocular manifestations of PNP can rarely present with spontaneous corneal perforations. This is the first case of FDCS-associated PNP with corneal involvement. Such cases should be diagnosed expediently and managed with aggressive systemic immunosuppressive therapy.

Exosomes have recently emerged as a pivotal mediator of many physiological and pathological processes. However, the role of exosomes in proliferative vitreoretinopathy (PVR) has not been reported. In this study, we aimed to investigate the role of exosomes in PVR. Transforming growth factor beta 2 (TGFß-2) was used to induce epithelial-mesenchymal transition (EMT) of retinal pigment epithelial (RPE) cells, as an in vitro model of PVR. Exosomes from normal and EMTed RPE cells were extracted and identified. We incubated extracted exosomes with recipient RPE cells, and co-cultured EMTed RPE cells and recipient RPE cells in the presence of the exosome inhibitor GW4869. Both experiments suggested that there are further EMT-promoting effects of exosomes from EMTed RPE cells. MicroRNA sequencing was also performed to identify the miRNA profiles in exosomes from both groups. We identified 34 differentially expressed exosomal miRNAs (P <. 05). Importantly, miR-543 was found in exosomes from EMTed RPE cells, and miR-543-enriched exosomes significantly induced the EMT of recipient RPE cells. Our study demonstrates that exosomal miRNA is differentially expressed in RPE cells during EMT and that these exosomal miRNAs may play pivotal roles in EMT induction. Our results highlight the importance of exosomes as cellular communicators within the microenvironment of PVR.