Aftermarket effects of cenegermin for neurotrophic keratopathy in pediatric patients

PurposeNeurotrophic keratopathy (NK) is a rare condition characterized by poor corneal sensation and healing. Cenegermin (topical recombinant nerve growth factor) has gained traction as a medical therapy for NK in recent years, and is FDA-approved for patients over two years old. However, no major trials have demonstrated the drug's efficacy in children. This study reviews the outcomes of cenegermin therapy in a pediatric patient population.MethodsRetrospective case series of patients from three tertiary referral institutions who 1) initiated an 8-week course of cenegermin therapy, and 2) were 18 years or less at time of treatment initiation.ResultsEight pediatric patients, with a total of nine affected eyes, underwent cenegermin therapy. All eight patients had previously trialed other NK-specific treatments, none of which had been entirely successful. Five patients (63%) completed the full eight-week therapy course. Five patients (63%) experienced clinical improvement not attributed to another treatment, through improved corneal ulcer stage (n = 5) and best-corrected visual acuity (n = 2). Clinical improvements persisted through a mean recurrence-free period of 10 months. Adverse effects reported during therapy included ocular pain, difficulty sleeping, and continued corneal thinning.ConclusionThe results provide modest support for the use of cenegermin in pediatric patients with neurotrophic keratopathy. The primary benefit was an improvement in corneal epithelial stability. Clinicians should be aware that pre-existing corneal scarring in NK may significantly limit the ability of cenegermin alone to improve visual acuity, and should closely monitor the corneal epithelial status during therapy in pediatric patients.     

A multicenter report of the use of plasma rich in growth factors (PRGF) for the treatment of patients with ocular surface diseases in North America

PurposeTo investigate the efficacy and safety of plasma rich in growth factors (PRGF) eyedrops in the management of patients with ocular surface diseases in North America.MethodsMulticenter interventional case series of patients using PRGF eyedrops for the first time. A cohort of patients was analyzed for corneal staining score at initial visit and at 3 months of therapy with PRGF. Another cohort responded to a 10-item questionnaire that evaluated patients' satisfaction and safety, which included the symptom assessment questionnaire in dry eye (SANDE) score, after 6 months of PRGF treatment.ResultsA total of 153 patients were analyzed. Of these, 102 were reviewed for corneal epitheliopathy and 99 patients responded to the questionnaire. The mean (±SD) age of the population was 63.7 ± 17 years and 72.5% were female. The clinical indications for PRGF usage were dry eye (60%), neurotrophic keratopathy (15%), dormant corneal ulcers (12%), limbal stem cell deficiency (10%), and cicatrizing conjunctivitis (4%). At the final visit, 74.3% of patients showed an improvement of their corneal staining. Those who had punctate epithelial erosions or epithelial defects were reduced from 76.5% to 47% and 23.5% to 7.8% respectively (p < 0.0001). Symptoms, measured via SANDE score, significantly decreased from a median of 90 to 34.6 out of 100 points on follow-up (p < 0.0001). Only one patient (0.98%) complained of ocular burning sensation as a side effect.ConclusionsThis multicentric study demonstrates the safety and efficacy of the use of PRGF for treating signs and symptoms in patients with significant ocular surface diseases.     

Investigation of factors associated with ABCB5-positive limbal stem cell isolation yields from human donors

PurposeTo identify factors associated with isolation yields of ATP-binding cassette (ABC) superfamily member B5 (ABCB5)-positive limbal stem cells (LSCs) from human cadaveric donor eyes.MethodsWhole eye globes were obtained from the Saving Sight eye bank, Kansas City, MO and the CorneaGen eye bank, Seattle, WA. ABCB5-positive LSCs were sorted by flow cytometry upon anti-ABCB5 monoclonal antibody staining within one week after donor death. The yields of live limbal epithelial cells in their entirety and of isolated pure ABCB5-positive LSC subsets were correlated with variables contained in the eye donors’ medical information.ResultsThe mean isolation yield of live limbal epithelial cells and ABCB5-positive LSCs per donor eye was (340,000 ± 160,000 and 2,608 ± 1,842 respectively, mean ± SD). Stepwise regression analysis showed that cardiac disease-related death was the strongest negative predictor of the ABCB5-positive LSC isolation yield (p = 0.01). While we observed a trend for an age-related decline in the yield of ABCB5-positive LSCs, a statistically significant association could not be established (2% decrease/year, p = 0.11). Additionally, despite a trend for decreased isolation yields of total live limbal epithelial cells isolated from single donors with a longer time between death and tissue processing (p = 0.04), this did not affect the yields of purified ABCB5-positive LSC, which was independent of increasing time between death and tissue processing (p = 0.50).ConclusionsOur study identifies cardiac disease-related death as a donor variable significantly associated with lower ABCB5-positive LSC isolation yields.     

Meibum sphingolipid composition is altered in individuals with meibomian gland dysfunction-a side by side comparison of Meibum and Tear Sphingolipids

PurposeSphingolipids (SPL) play a role in cell signaling, inflammation, and apoptosis. The purpose of this study was to examine meibum and tear SPL composition in individuals with poor versus good meibum quality.MethodsIndividuals were grouped by meibum quality (n = 25 with poor quality, case group and n = 25 with good quality, control group). Meibum and tears were analyzed with liquid chromatography-mass spectrometry (LC-MS) to quantify SPL classes. Semiquantitative and relative composition (mole percent) of SPL and major classes, Ceramide (Cer), Hexosyl-Ceramide (Hex-Cer), Sphingomyelin (SM), Sphingosine (Sph), and sphingosine 1-phosphate (S1P) were compared between groups.ResultsDemographic characteristics were similar between the two groups. Overall, individuals with poor meibum quality had more SPL pmole in meibum and tears than controls. Relative composition analysis revealed that individuals with poor meibum quality had SPL composed of less Cer, Hex-Cer, and Sph and more SM compared to individuals with good quality meibum. This pattern was not reproduced in tears as individuals with poor meibum quality had SPL composed of a similar amount of Cer, but more Hex-Cer, Sph and SM compared to controls. In meibum, SPL pmole and relative composition most strongly correlated with MG metrics while in tears, SPL pmole and relative composition most strongly correlated with tear production. SPL in both compartments, specifically Cer pmole in meibum and S1P% in tears, correlated with DE symptoms.ConclusionSPL composition differs in meibum and tears in patients with poor vs good meibum quality. These findings may be translated into therapeutic targets for disease.     

Visualization of microneuromas by using in vivo confocal microscopy: An objective biomarker for the diagnosis of neuropathic corneal pain?

PurposeThe diagnosis of neuropathic corneal pain (NCP) is challenging, as it is often difficult to differentiate it from conventional dry eye disease (DED). In addition to eye pain, NCP can present with similar signs and symptoms of DED. The purpose of this study is to find an objective diagnostic sign to identify patients with NCP, using in vivo confocal microscopy (IVCM).MethodsThis was a comparative, retrospective, case-control study. Patients with clinical diagnosis of NCP (n = 25), DED (n = 30), and age- and sex-matched healthy controls (n = 16), who underwent corneal imaging with IVCM (HRT3/RCM) were included. Central corneal IVCM scans were analyzed by 2 masked observers for nerve density and number, presence of microneuromas (terminal enlargements of subbasal corneal nerve) and/or nerve beading (bead-like formation along the nerves), and dendritiform cell (DC) density.ResultsThere was a decrease in total nerve density in both NCP (14.14 ± 1.03 mm/mm²) and DED patients (12.86 ± 1.04 mm/mm²), as compared to normal controls (23.90 ± 0.92 mm/mm²; p < 0.001). However, total nerve density was not statistically different between NCP and DED patients (p = 0.63). Presence of nerve beading was not significantly different between patients and normal controls (p = 0.15). Interestingly, microneuromas were observed in all patients with NCP, while they were not present in any of the patients with conventional DED (sensitivity and specificity of 100%). DC density was significantly increased in both NCP (71.89 ± 16.91 cells/mm²) and DED patients (111.5 ± 23.86 cells/mm²), as compared to normal controls (24.81 ± 4.48 cells/mm² (p < 0.05). However, there was no significant difference in DC density between DED and NCP patients (p = 0.31).ConclusionIVCM may be used as an adjunct diagnostic tool for the diagnosis of NCP in the presence of neuropathic symptoms. Microneuromas may serve as a sensitive and specific biomarker for the diagnosis of NCP.     

Dry eye signs and symptoms in aromatase inhibitor treatment and the relationship with pain

PurposeAromatase inhibitors (AIs) limit the synthesis of oestrogen in peripheral tissues thus lowering levels of oestrogen. The primary aim was to evaluate whether women treated with AIs have altered dry eye symptoms and signs. A sub-aim was to investigate whether symptoms of dry eye in postmenopausal women were associated with symptoms of non-eye pain, ocular pain and self-rated pain perception.MethodsThis cross-sectional, observational, single visit study recruited 56 postmenopausal women (mean age 64.1 + 7.9 years) and 52 undergoing AI treatment (mean age 66.6 + 9.0). Ocular symptoms (OSDI, MGD14) and pain questionnaires (PSQ, OPAS) were administered and signs of dry eye and meibomian gland dysfunction were evaluated.ResultsAlmost half of each group reported dry eye symptoms, defined as OSDI>12 (48% control, 46% AI). The PSQ score was significantly higher in the AI group (p = 0.04). Neither frequency or severity of dry eye (or MGD) symptoms scores were significantly different between groups. In the AI group, meibomian gland expressibility score was worse (p = 0.003); there were no differences in any other signs. Higher OSDI scores were associated with higher OPAS eye-pain scores (r = 0.49, p < 0.001), but not OPAS non-eye pain (r = 0.09, p = 0.35). Pain perception (PSQ) showed a moderate positive association with OPAS eye-pain (r = 0.30, p = 0.003).ConclusionsIn this study elevated ocular symptoms were observed in both the AI treated and the untreated groups, with no difference between the groups. Women undergoing AI treatment for early stage breast cancer had worse meibum expressibility score and increased pain perception compared to an untreated group of women.     

DryEyeRhythm: A reliable and valid smartphone application for the diagnosis assistance of dry eye

PurposeUndiagnosed or inadequately treated dry eye disease (DED) decreases the quality of life. We aimed to investigate the reliability, validity, and feasibility of the DryEyeRhythm smartphone application (app) for the diagnosis assistance of DED.MethodsThis prospective, cross-sectional, observational, single-center study recruited 82 participants (42 with DED) aged ≥20 years (July 2020–May 2021). Patients with a history of eyelid disorder, ptosis, mental disease, Parkinson's disease, or any other disease affecting blinking were excluded. Participants underwent DED examinations, including the Japanese version of the Ocular Surface Disease Index (J-OSDI) and maximum blink interval (MBI). We analyzed their app-based J-OSDI and MBI results. Internal consistency reliability and concurrent validity were evaluated using Cronbach's alpha coefficients and Pearson's test, respectively. The discriminant validity of the app-based DED diagnosis was assessed by comparing the results of the clinical-based J-OSDI and MBI. The app feasibility and screening performance were evaluated using the precision rate and receiver operating characteristic curve analysis.ResultsThe app-based J-OSDI showed good internal consistency (Cronbach's α = 0.874). The app-based J-OSDI and MBI were positively correlated with their clinical-based counterparts (r = 0.891 and r = 0.329, respectively). Discriminant validity of the app-based J-OSDI and MBI yielded significantly higher total scores for the DED cohort (8.6 ± 9.3 vs. 28.4 ± 14.9, P < 0.001; 19.0 ± 11.1 vs. 13.2 ± 9.3, P < 0.001). The app's positive and negative predictive values were 91.3% and 69.1%, respectively. The area under the curve (95% confidence interval) was 0.910 (0.846–0.973) with concurrent use of the app-based J-OSDI and MBI.ConclusionsDryEyeRhythm app is a novel, non-invasive, reliable, and valid instrument for assessing DED.     

Infrared meibography allows detection of dimensional changes in meibomian glands following intranasal neurostimulation

PurposePatients with dry eye disease (DED) may suffer from decreased tear break-up time due to meibomian gland (MG) dysfunction. Infrared meibography (IR Meibography) uses infrared wavelength light to visualize meibomian glands in vivo. We aimed to explore the feasibility of using serial IR Meibography imaging to assess morphological changes in MGs as an indirect measure of functionality, following intranasal neurostimulation (ITN).MethodsFifteen DED subjects were prospectively enrolled in a single-center, single-arm study. Changes in MGs were captured using IR meibography (RTVUE-XR, Optovue, Inc. Fremont, CA, USA) on the lower eyelids before and after 3 min of ITN (TrueTear®, Allergan, Dublin, Ireland) use that delivers a microcurrent to sensory neurons of the nasal cavity. The same MGs were selected pre- and post-stimulation, and MG area and perimeter were analyzed by two masked observers.ResultsMean (±SD) pre- and post-stimulation MG areas were 2,187.60 ± 635.88 μm² and 1,933.20 ± 538.55 μm², respectively. The mean change in area, 254.49 μm², representing an 11.6% reduction following ITN use, was statistically significant (p = 0.001). Mean (±SD) pre- and post-stimulation MG perimeters were 235.9 ± 51.38 μm and 222.2 ± 47.72 μm, respectively. The mean change in perimeter, 13.7 μm, representing a 5.81% reduction following ITN use, was statistically significant (p = 0.012).ConclusionsOur study shows that IR meibography can be used to detect immediate changes in gland area and perimeter, an indirect measure of MG activity following intervention by ITN.     

Cultivated Limbal and Oral Mucosal Epithelial Transplantation

Stem cells located at the limbus are the ultimate source for regeneration of the corneal epithelium in normal and traumatized states. When limbal stem cells are dysfunctional or deficient, limbal stem cell deficiency (LSCD) develops. Its surgical management depends on laterality and severity of corneal-limbal involvement. Conventional methods of stem cell transplantation are conjunctival-limbal autograft (CLAU), conjunctival-limbal allograft (CLAL), and kerato-limbal allograft (KLAL) surgeries. Cultivated limbal epithelial transplantation (CLET) and cultivated oral mucosal epithelial transplantation (COMET) on a carrier such as amniotic membrane are current surgical alternatives. These new surgical procedures are effective in stabilizing the ocular surface. The theoretical advantage of ex-vivo expansions over conventional methods is that only a small limbal or mucosal biopsy is needed, thus minimizing the risk to the donor eye; there is also a lower risk of rejection. They can be used in cases with unilateral or bilateral total stem cell deficiency. In the unilateral cases, the source for CLET is a healthy fellow eye and in bilateral cases the source can be living-related or cadaveric eyes. The oral explants do not have limbal stem cells, but they seem to be a source of limbal stem cell equivalents that are able to generate cornea-like epithelium under the proper culture conditions. The main advantage of COMET is that patients with bilateral LSCD can be treated with grafts derived from their own autologous oral mucosal cells. The long-term outcomes of COMET have to be elucidated.     

Benzalkonium chloride,a common ophthalmic preservative,compromises rat corneal cold sensitive nerve activity

PurposeCorneal nerves comprise the densest sensory network in the body. Dysfunction of the corneal cold sensitive neurons (CSN) is implicated in ophthalmic disorders, including Dry Eye Disease, the most common ocular surface disorder. The preservative Benzalkonium chloride (BAK) and the mydriatic agent Phenylephrine hydrochloride (PHE) are considered to be inactive at the level of the CSNs. The purpose of this study is to test the impacts of continuous exposures to BAK or PHE at their clinically used concentrations on corneal nerve structure and function.MethodsIn vivo extracellular electrophysiology of the rat trigeminal ganglion was used to monitor CSN functional response to stimuli mimicking physiological states and stressors of the cornea. Corneal nerve structure was evaluated by immunostaining.ResultsAmong the tested stimuli, cold probe receptive field stimulation and hyperosmolar stress were the most sensitive methods of detecting activity changes. CSN activity was attenuated after 30 min exposure to either PHE or BAK. After an hour-long washout period, BAK-treated neurons failed to recover activity while PHE-treated neurons showed signs of functional recovery. Intraepithelial nerve density was reduced and nerve fragmentation was increased in BAK-treated corneas, while PHE exposure left corneal nerves structurally intact.ConclusionsOur study suggests that prolonged ocular instillations of BAK or PHE alter CSN activity through two different processes — irreversible neuronal damage in the case of BAK vs. reversible attenuation in the case of PHE.     

Alterations in corneal nerves in different subtypes of dry eye disease: An in vivo confocal microscopy study

PurposeTo evaluate corneal subbasal nerve alterations in evaporative and aqueous-deficient dry eye disease (DED) as compared to controls.MethodsIn this retrospective, cross-sectional, controlled study, eyes with a tear break-up time of less than 10 s were classified as DED. Those with an anesthetized Schirmer's strip of less than 5 mm were classified as aqueous-deficient DED. Three representative in vivo confocal microscopy images were graded for each subject for total, main, and branch nerve density and numbers.ResultsCompared to 42 healthy subjects (42 eyes), the 70 patients with DED (139 eyes) showed lower total (18,579.0 ± 687.7 μm/mm² vs. 21,014.7 ± 706.5, p = 0.026) and main (7,718.9 ± 273.9 vs. 9,561.4 ± 369.8, p < 0.001) nerve density, as well as lower total (15.5 ± 0.7/frame vs. 20.5 ± 1.3, p = 0.001), main (3.0 ± 0.1 vs. 3.8 ± 0.2, p = 0.001) and branch (12.5 ± 0.7 vs. 16.5 ± 1.2, p = 0.004) nerve numbers. Compared to the evaporative DED group, the aqueous-deficient DED group showed reduced total nerve density (19,969.9 ± 830.7 vs. 15,942.2 ± 1,135.7, p = 0.006), branch nerve density (11,964.9 ± 749.8 vs. 8,765.9 ± 798.5, p = 0.006), total nerves number (16.9 ± 0.8/frame vs. 13.0 ± 1.2, p = 0.002), and branch nerve number (13.8 ± 0.8 vs. 10.2 ± 1.1, p = 0.002).ConclusionsPatients with DED demonstrate compromised corneal subbasal nerves, which is more pronounced in aqueous-deficient DED. This suggests a role for neurosensory abnormalities in the pathophysiology of DED.     

Cytomorphological assessment of the lid margin in relation to symptoms,contact lens wear and lid wiper epitheliopathy

Purpose: Lid wiper epitheliopathy (LWE) is insufficiently understood from a cytological perspective. This study explored the relationship between lid margin cytomorphology, LWE, contact lens wear, and lens-related symptoms.Methods: Habitual, symptomatic (n = 20) and asymptomatic (n = 20) soft, rigid gas permeable (n = 18) and non-contact lens wearers (n = 19) were enrolled. LWE was graded using lissamine green and the Korb scale. Subjective symptoms were assessed using the Ocular Surface Disease Index and the Contact Lens Dryness Evaluation Questionnaire. Impression cytology samples obtained from the central upper and lower lid margins of both eyes stained histologically to highlight keratinization and imaged using high-resolution microscopy. A masked investigator digitally delimited and measured the average sagittal width of the lid wiper conjunctiva and mucocutaneous junction using ImageJ. Results:The upper lid wiper conjunctiva measured 424 ± 171 μm, 404 ± 75, 667 ± 219 and 266 ± 64 in asymptomatic soft, symptomatic soft, rigid and non-contact lens wearers, respectively. The corresponding lower lid wiper conjunctivae measured 141 ± 57 μm, 232 ± 150, 519 ± 212 and 225 ± 102, which was significantly narrower than that of the upper eyelid in most cases (p < 0.05). Symptoms were not associated with lid margin changes; however, rigid lens wear and clinical LWE were associated with histologically enlarged lid wiper conjunctival areas and increased keratinization.Conclusion: A novel, exploratory account of histological measures of LWE and cytomorphological change associated with contact lens wear suggests mechanical or frictional cellular insult is occurring at the lid wiper conjunctiva.     

Factores asociados al desprendimiento de retina pseudofáquico: seguimiento a largo plazo en una población colombiana

ObjectiveTo identify associated factors with the appearance of pseudophakic retinal detachment in patients with history of cataract surgery.MethodsRetrospective case–control study of 802 eyes of 783 patients with history of cataract surgery. Cases were patients with pseudophakic retinal detachment (n = 258 eyes), while controls were patients with cataract surgery who did not developed retinal detachment during a 10-year follow-up period (n = 544 eyes).ResultsAge at cataract surgery among cases was lower than in the control group (57 ± 13 vs. 67 ± 14 years old, respectively; P < .0001). Age at retinal detachment was 59 ± 13 years old (range 6–88) and the time between the cataract surgery and the retinal detachment had a median of 2 years (interquartile range 1–4) with a range of 1 month to 14 years. Associated factors for pseudophakic retinal detachment were younger age (< 50 years: adjusted odds ratio [aOR] = 18.03, 95% confidence interval [95% CI] = 5.92–54.87; 50–59 years: aOR = 10.09, 95% CI = 3.37–30.23; and 60–69 years: aOR = 5.48, 95% CI = 1.88–15.93), male sex (aOR = 3.71, 95% CI = 2.54–5.44), anterior vitrectomy (aOR = 3.26, 95% CI = 1.16–9.16), history of retinal detachment in the fellow eye (aOR = 6.95, 95% CI = 3.15–15.31), and intraoperative complications during cataract extraction (aOR = 7.45, 95% CI = 3.54–15.69).ConclusionsThis is the first report of associated factors with pseudophakic retinal detachment in a Colombian population. Surgical complications, sex, and age were found to be associated with retinal detachment. Patients should be aware of these potential risks to make informed decisions about their eye health.     

The Dry Eye Assessment and Management (DREAM) extension study – A randomized clinical trial of withdrawal of supplementation with omega-3 fatty acid in patients with dry eye disease

PurposeTo determine effects of continued or discontinued use of omega-3 (ω3) fatty acid supplements through a randomized withdrawal trial among patients assigned to ω3 supplements in the first year of the DREAM study.MethodsPatients who were initially assigned to ω3 (3000 mg) for 12 months in the primary trial were randomized 1:1 to ω3 active supplements or placebos (refined olive oil) for 12 more months. The primary outcome was change in the Ocular Surface Disease Index (OSDI) score. Secondary outcomes included change in conjunctival staining, corneal staining, tear break-up time, Schirmer test, and adverse events.ResultsAmong 22 patients assigned to ω3 and 21 to placebo supplements, the mean change in OSDI score between month 12 and 24 was similar between treatment groups (mean difference in change −0.6 points, 95% confidence interval [CI], (−10.7, 9.5), p = 0.91). There were no significant differences between groups in mean change in conjunctival staining (difference in mean change −0.5 points; 95% CI (−1.2, 0.3)), corneal staining (−0.3 points; 95% CI (−1.2, 0.3)), tear break-up time (−0.8 s; 95% CI (−2.6, 0.9)) and Schirmer test (0.6 mm, 95% CI (−2.0, 3.2)). Rates of adverse events were similar in both groups.ConclusionAmong patients who received ω3 supplements for 12 months in the primary trial, those discontinuing use of ω3 for an additional 12 months did not have significantly worse outcomes compared to those who continued use of ω3.ClinicalTrials.gov number NCT02128763.     

Neuronal-epithelial cell alignment: A determinant of health and disease status of the cornea

PurposeHow sensory neurons and epithelial cells interact with one another, and whether this association can be considered an indicator of health or disease is yet to be elucidated.MethodsHerein, we used the cornea, Confetti mice, a novel image segmentation algorithm for intraepithelial corneal nerves which was compared to and validated against several other analytical platforms, and three mouse models to delineate this paradigm. For aging, eyes were collected from 2 to 52 week-old normal C57BL/6 mice (n ≥ 4/time-point). For wound-healing and limbal stem cell deficiency, 7 week-old mice received a limbal-sparing or limbal-to-limbal epithelial debridement to their right cornea, respectively. Eyes were collected 2–16 weeks post-injury (n=4/group/time-point), corneas procured, immunolabelled with βIII-tubulin, flat-mounted, imaged by scanning confocal microscopy and analyzed for nerve and epithelial-specific parameters.ResultsOur data indicate that nerve features are dynamic during aging and their curvilinear arrangement align with corneal epithelial migratory tracks. Moderate corneal injury prompted axonal regeneration and recovery of nerve fiber features. Limbal stem cell deficient corneas displayed abnormal nerve morphology, and fibers no longer aligned with corneal epithelial migratory tracks. Mechanistically, we discovered that nerve pattern restoration relies on the number and distribution of stromal-epithelial nerve penetration sites.ConclusionsMicrostructural changes to innervation may explain corneal complications related to aging and/or disease and facilitate development of new assays for diagnosis and/or classification of ocular and systemic diseases.     

Neurotrophic keratitis: Frequency,etiologies, clinical management and outcomes

PurposeTo determine neurotrophic keratitis (NK) frequency, etiologies and prognostic factors, and evaluate the outcome of its management.MethodsIn this retrospective epidemiologic study, we reviewed the electronic records of all patients consulting our tertiary referral eye hospital between November 2009 and October 2017. NK was defined as corneal hypoesthesia or anesthesia associated with epithelial irregularities.ResultsAmong the 305,351 patients’ files screened for eligibility, 335 (354 eyes) were included, yielding an NK frequency of 11/10,000 (0.11%). Their mean ± SD age was 63.1 ± 21.0 years. Eyes were equally divided among the Mackie classification 3 stages. The most frequent etiology was herpetic eye disease (114 eyes; 32.2%). A multifactorial cause was found for 121 (34.2%) eyes. Surgery required for 118 eyes (33.3%). Respective success rates for amniotic membrane transplantation (AMT) or matrix-regeneration of stages 2 and 3, and autologous serum of stage 1 were 57.2%, 63.6% and 21.7%, with mean healing times of 15.0, 16.3 and 85 days. The overall healing rate was 79.5%, with a mean of 44.8 days to healing. Advanced initial stage, diminished corrected-distance visual acuity (CDVA) and advanced age correlated with worse final CDVA.ConclusionsNK was more frequent than previously reported in the literature. Delayed diagnoses indicated we must increase ophthalmologists’ awareness of this disease for patients with decreased corneal sensitivity and abnormal epithelium. To improve prognosis and final CDVA, NK-specific treatment should be initiated as soon as the diagnosis is suspected. Patient-centered combinations of different therapeutic components and close monitoring achieved promising results.     

Association between dry eye and depressive symptoms: Large-scale crowdsourced research using the DryEyeRhythm iPhone application

PurposeDry eye (DE) disease and depression are increasing in modern times. We investigated the association between DE and depressive symptoms using the iPhone application, DryEyeRhythm.MethodsThis large-scale crowdsourced observational study was conducted within iPhone users in Japan who downloaded DryEyeRhythm. Participants with a Zung Self-rating Depression Scale (SDS) score ≥ 40 were defined as having depressive symptoms, and those with an Ocular Surface Disease Index (OSDI) score ≥ 13 were defined as having DE symptoms (mild, 13–22; moderate, 23–32; and severe, 33–100). We compared SDS scores between participants with normal eye and mild, moderate, and severe OSDI-based DE symptoms. Logistic regression analyses were used to determine the association between DE severity and depressive symptoms after adjustment for demographic characteristics, medical history, and lifestyle habits.ResultsThis study included 4454 participants (mean age, 27.9 ± 12.6 years; female, 66.7%). Participants with SDS scores ≥40 accounted for 58.2%, 70.9%, 79.4%, and 85.0% of normal controls and participants with mild, moderate, and severe DE symptoms, respectively (P trend < 0.001). The adjusted odds ratios (95% confidence interval) for depressive symptoms (SDS score of ≥40) were 1.62 (1.35–1.95) for mild, 2.39 (1.92–2.97) for moderate, and 3.29 (2.70–4.00) for severe DE symptoms.ConclusionThis large-scale crowdsourced clinical study using DryEyeRhythm suggests that depressive symptoms are more common in individuals with more severe DE symptoms. DryEyeRhythm could play a role in earlier prevention or future prospective interventions for depressive symptoms in individuals with DE symptoms.     

Membrane-associated mucins of the ocular surface: New genes,new protein functions and new biological roles in human and mouse

The mucosal glycocalyx of the ocular surface constitutes the point of interaction between the tear film and the apical epithelial cells. Membrane-associated mucins (MAMs) are the defining molecules of the glycocalyx in all mucosal epithelia. Long recognized for their biophysical properties of hydration, lubrication, anti-adhesion and repulsion, MAMs maintain the wet ocular surface, lubricate the blink, stabilize the tear film and create a physical barrier to the outside world. However, it is increasingly appreciated that MAMs also function as cell surface receptors that transduce information from the outside to the inside of the cell. A number of excellent review articles have provided perspective on the field as it has progressed since 1987, when molecular cloning of the first MAM was reported. The current article provides an update for the ocular surface, placing it into the broad context of findings made in other organ systems, and including new genes, new protein functions and new biological roles. We discuss the epithelial tissue-equivalent with mucosal differentiation, the key model system making these advances possible. In addition, we make the first systematic comparison of MAMs in human and mouse, establishing the basis for using knockout mice for investigations with the complexity of an in vivo system. Lastly, we discuss findings from human genetics/genomics, which are providing clues to new MAM roles previously unimagined. Taken together, this information allows us to generate hypotheses for the next stage of investigation to expand our knowledge of MAM function in intracellular signaling and roles unique to the ocular surface.