Incidence of Retinal Detachment, Macular Edema, and Ocular Hypertension after Neodymium:Yttrium-Aluminum-Garnet Capsulotomy: A Population-Based Nationwide Study-The French YAG 2 Study.

PURPOSE: To estimate the incidence and assess the risk factors associated with 3 adverse events (AEs) after neodymium:yttrium-aluminum-garnet posterior capsulotomy (Nd:YAG-caps): ocular hypertension (OHT), macular edema (ME), and retinal detachment (RD). DESIGN: Observational cohort study using a nationwide claims database. PARTICIPANTS: Adults who underwent Nd:YAG-caps between 2014 and 2017, with no ocular disease history in the year before. METHODS: Patients who underwent Nd:YAG-caps were identified using data from the French national representative sample and followed up for 12 months postprocedure. The time to AE was assessed using the Kaplan-Meier method. Factors associated with AE were assessed using Cox models. MAIN OUTCOME MEASURES: Neodymium:YAG-caps epidemiology, patients' characteristics, proportion of patients with AE, and hazard ratios (HRs) associated with variables identified as factors associated with AEs. RESULTS: During the study period, 6210 patients received Nd:YAG-caps (7958 procedures). The mean age (± standard deviation) at Nd:YAG-caps was 75.0 (± 10.3) years. The 3-month and 12-month overall AE rates (≥ 1 AE of interest) were 8.6% and 13.3%, respectively. Among patients with ≥ 1 AE of interest, 68.4% of AEs occurred within 3 months post-Nd:YAG-caps. Three-month rates were ≈5% for OHT and ME. Retinal detachment remained ≤ 0.5% over follow-up. Cox models showed that patients with Nd:YAG-caps performed within 1 year after cataract surgery had a higher risk of AEs than those with later Nd:YAG-caps (hazard ratio [HR], 1.314 [1.034-1.669], P = 0.0256), notably ME (HR, 1.500 [1.087-2.070], P = 0.0137). Diabetic patients were more at risk of OHT (HR, 1.233 [1.005-1.513], P = 0.0448) and ME (HR, 1.810 [1.446-2.266], P < 0.0001) than nondiabetic patients. Patients with Nd:YAG-caps performed between 1 and 2 years after cataract surgery were more at risk of OHT than patients with later Nd:YAG-caps (HR, 1.429 [1.185-1.723], P = 0.0002). CONCLUSIONS: According to a national claims database, OHT and ME were the most frequent AEs of interest post-Nd:YAG-caps, mainly observed within 3 months postprocedure, highlighting the need for a close follow-up during this period or a delayed capsulotomy. Diabetes and an early Nd:YAG-caps after cataract surgery were among the main drivers for AE occurrence. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Incidence of Nd:YAG laser capsulotomy following cataract surgery: a population-based nation-wide study - FreYAG1 study.

RATIONALE: Nd:YAG (neodymium:yttrium-aluminum-garnet) capsulotomy (Nd:YAG-caps) is the gold standard for the treatment of PCO (Posterior Capsule Opacification). There is a lack of real-world data about Nd:YAG-caps use. PURPOSE: This study's objectives were to estimate Nd:YAG-caps incidence in France, to describe the patient characteristics, and to analyze the time between surgeries and capsulotomies. SETTING: The study was based on data extracted from the EGB database, a 1/97th sample representative of the French population. DESIGN: observational, retrospective, cohort study using national claims data. METHODS: French adult patients who underwent Nd:YAG-caps between 2014 and 2017 were selected. Main outcomes were the number of patients and procedures performed and the risk factors associated with early Nd:YAG-caps. RESULTS: During the study period, Nd:YAG-caps were performed in 8,425 patients accounting for 10,774 procedures. The extrapolation to the French population led to estimate that 253.103 patients had Nd:YAG-caps, representing 312.103 procedures in 2017. The mean age at Nd:YAG-caps was 75.1 (± 10.2) years. About 36% of patients presented at least one ocular comorbidity. Nd:YAG-caps was performed within 2 years after surgery in 33.0% of patients and within one year in 9.8% of patients. Patients with Nd:YAG-caps within the first year (OR CI95 0.721 [0.673-0.772]) or in the first two years (OR CI95 0.721 [0.673-0.772]) were younger than patients with later Nd:YAG-caps and had a more frequent history of treated ocular diseases (OR 1.516 and 1.178, respectively). CONCLUSIONS: This study brought new real-world and large-scale data regarding Nd:YAG-caps use and gave an updated insight into the patients' characteristics.

Severe macular complications in glaucoma: high-resolution multimodal imaging characteristics and review of the literature.

PURPOSE: To describe imaging characteristics of severe macular complications occurring in glaucoma and discuss available treatments. METHODS: Retrospective case series of glaucomatous patients with macular retinoschisis (MR) and/or serous retinal detachment (SRD). Patients underwent a complete ophthalmological examination and multimodal imaging including retinography, SD-OCT, fluorescein and indocyanine green angiography (FA & ICGA) and adaptive optics (AO). RESULTS: Ten eyes (8 patients) were included. Initial BCVA was 1.04 ± 1.12 logMAR and IOP was 24.0 ± 9.3mmHg. All eyes presented with MR while SRD was present in 5 eyes (5 patients), with a central macular thickness of 573 ± 152 µm. FA and ICGA allowed to exclude leakage in all cases. A focal lamina cribrosa defect (LCD) was found in four eyes (4 patients) using OCT, with AO providing en-face visualization of the defect in one eye. Outer retinal hole was present in 3 eyes (3 patients). No visual improvement or resolution of the macular retinoschisis was observed in eyes with medical or surgical IOP control (N = 9). Vitrectomy with internal membrane limiting peeling and gas tamponade was performed in one eye with good visual results. CONCLUSIONS: Multimodal high-resolution imaging is essential to diagnose severe macular complications associated with advanced glaucoma.

Effect of artificial tears on dynamic optical quality in patients with dry eye disease.

BACKGROUND: In clinical practice, fluctuating vision or decreased quality of vision is a common complaint in DED patients. Our study was designed to investigate the change in dynamic optical quality in dry eye patients after the use of artificial tears. METHODS: Fifty-nine patients with dry eye disease (DED) and 31 control subjects were included in this prospective case-control study. There was no significant difference in age and sex between these two groups (P = 0.342, P = 0.847, respectively). Clinical evaluation of the ocular surface included Ocular Surface Disease Index (OSDI), tear film break-up time (TBUT), lipid layer thickness (LLT), and Schirmer I test. DED patients were divided into two groups, mild (31 patients) and severe (28 patients). The optical quality of the tear film was measured with the Optical Quality Analysis System (OQAS) using the mean objective scatter index (mean OSI), standard deviation of objective scatter index (SD-OSI) and modulation transfer function cut-off (MTF cut-off). After baseline examinations, one drop of artificial tears (ATs, carboxymethylcellulose ophthalmic solution, 0.5%) was instilled in both eyes, and optical quality parameters were measured again at 5 and 30 min following application of ATs. RESULTS: At baseline, the mean OSI was higher in the DED group (0.95 ± 0.54) than in controls (0.54 ± 0.23, P < 0.001). The SD-OSI was also significantly increased in DED patients (0.44 ± 0.71) compared to control subjects (0.12 ± 0.06, P = 0.003). Five minutes after AT instillation, mean OSI and SD-OSI decreased significantly in severe DED patients (P = 0.044; P = 0.018), remained unchanged in mild DED patients, and increased in the control group (P = 0.019; P < 0.001). Thirty minutes after AT instillation, no significant difference in optical quality parameters was observed among the three groups. CONCLUSION: The effect of ATs on optical quality in patients with DED may differ according to the severity of the disease. Measurement of optical quality might be a promising tool to evaluate the effects of various ATs and possibly individualize treatment in DED patients.

Driving behaviour and visual compensation in glaucoma patients: Evaluation on a driving simulator.

BACKGROUND: To assess the driving performance and both the visual scanning and driving compensations of glaucoma patients. METHODS: In this case-control pilot study, the driving behaviour and performance of 14 patients with glaucoma and nine healthy age- and sex-similar control subjects were compared in a fixed-base driving simulator. All subjects performed in four scenarios with one to two hazardous situations on urban streets, for a total of five hazards. Measurements taken during the tests included reaction times, longitudinal regulation, lateral control and eye and head movements. RESULTS: Glaucoma patients showed poor driving performance with longer reaction time to hazardous situations than control subjects: pedestrians crossing the road from the left (p < 0.022) or from the right (p = 0.013), and vehicles coming from the left (p = 0.002). Their mean duration of lateral excursion was longer (p = 0.045), and they showed more lane excursions in a wide left curve (p = 0.045). Glaucoma patients also showed a higher standard deviation of time-headway (p = 0.048) with preceding vehicles. Analyses of driving behavioural compensations on curved roads showed that glaucoma patients stayed closer to the centre line in large (p = 0.006) and small (p = 0.025) left curves and on small right curves (p = 0.041). Additionally, on straight roads, as compared to control subjects, glaucoma patients showed longer mean time-headway (p = 0.032) and lower mean speed (p = 0.04). Finally, the glaucoma group exhibited a larger standard deviation of horizontal gaze (p = 0.034) than the control subjects. CONCLUSIONS: In a virtual driving environment, glaucoma patients exhibited unsafe driving behaviours, despite their driving and eye-scanning compensations.

Lipoid Proteinosis presenting as beaded papules of the eyelid: report of three cases.

BACKGROUND: Lipoid proteinosis (LP) is a rare multisystem inherited disease. We report here in three LP cases with beaded papules of the eyelid. Their clinical presentations, histological characteristics, and genetic findings are described and discussed. CASE PRESENTATION: A 12-year-old boy reported to our hospital with a complaint of ocular irritation, redness, and tearing for two years. He had a history of hoarseness since childhood. His younger brother (5 years old) also complained of hoarseness. Another patient, a 26-year-old woman, described many beaded papules on the edge of her eyelids since age 11 years. She additionally reported hoarseness since 4 years of age. Careful slit-lamp examination in these cases revealed waxy beaded papules on the margins of both eyelids and mild conjunctival congestion. Physical examination showed irregular, rugged scars on their facial skin. Genetic analysis showed the mutation located in exon 6 of the ECM1 gene. CONCLUSIONS: Three LP cases first diagnosed by ophthalmologists are presented. The presence of eyelid papules should prompt the ophthalmologist to pay close attention to the patient's voice. If there is a definite history of hoarseness, these patients should undergo gene sequence analysis. If necessary, otorhinolaryngology and dermatology consults may help confirm the diagnosis. Treatment is primarily symptomatic to improve patients' quality of life.

PreserFlo MicroShunt® exposure: a case series.

BACKGROUND: PreserFlo® MicroShunt (PM) (also known as InnFocus® MicroShunt) is a subconjunctival stent implanted ab externo via a minimally invasive surgical procedure. The current indication is progressive, mild to moderate, open angle glaucoma uncontrolled on topical medications. According to the literature, adverse events are rare, mild and transient. CASE PRESENTATION: Two cases of stand-alone PreserFlo MicroShunt® implantation in patients with uncontrolled open-angle glaucoma are reported. Exposure occurred 7 days and 3 months respectively after implantation. These cases shared common features including preexisting blepharitis and the lack of a Tenon's flap. In both cases, removal of the device was required after several attempts at repair. CONCLUSIONS: PreserFlo MicroShunt® exposure is a potentially vision-threatening complication because of the risk of endophthalmitis. Potential risk factors include the absence of a Tenon's flap and pre-existing ocular surface inflammation. Ocular surface inflammation should be detected and treated prior to PM implantation. If a deficiency in Tenon's capsule is noted intraoperatively, close monitoring should be performed because of the higher risk of PM exposure.

Deep learning versus ophthalmologists for screening for glaucoma on fundus examination: A systematic review and meta-analysis.

BACKGROUND: In this systematic review and meta-analysis, we aimed to compare deep learning versus ophthalmologists in glaucoma diagnosis on fundus examinations. METHOD: PubMed, Cochrane, Embase, ClinicalTrials.gov and ScienceDirect databases were searched for studies reporting a comparison between the glaucoma diagnosis performance of deep learning and ophthalmologists on fundus examinations on the same datasets, until 10 December 2020. Studies had to report an area under the receiver operating characteristics (AUC) with SD or enough data to generate one. RESULTS: We included six studies in our meta-analysis. There was no difference in AUC between ophthalmologists (AUC = 82.0, 95% confidence intervals [CI] 65.4-98.6) and deep learning (97.0, 89.4-104.5). There was also no difference using several pessimistic and optimistic variants of our meta-analysis: the best (82.2, 60.0-104.3) or worst (77.7, 53.1-102.3) ophthalmologists versus the best (97.1, 89.5-104.7) or worst (97.1, 88.5-105.6) deep learning of each study. We did not retrieve any factors influencing those results. CONCLUSION: Deep learning had similar performance compared to ophthalmologists in glaucoma diagnosis from fundus examinations. Further studies should evaluate deep learning in clinical situations.

Influence of automated visual field testing on intraocular pressure.

BACKGROUND: To evaluate the influence of automated visual field (VF) testing on intraocular pressure (IOP) in patients with ocular hypertension (OHT) or glaucoma. METHODS: We conducted a prospective observational study in the glaucoma department at Quinze-Vingts National Ophthalmology Hospital in Paris. Ninety-five right eyes of 95 patients followed for glaucoma or OHT were included. IOP was measured three times using a Nidek NT-510 non-contact tonometer within a maximum of 5 min before and after VF testing. Sub analyses using logistic regression analysis were performed to evaluate the impact of gender, age, central corneal thickness (CCT), mean deviation (MD) of the VF, VF test duration and filtration surgery on IOP fluctuations. RESULTS: There was no significant change in IOP after VF testing, with IOP's 15.14 ± 4.00 mmHg before and 14.98 ± 3.33 mmHg after the VF (P = 0.4). The average change in IOP was 0.15 ± 1.82 mmHg. Using multivariate analysis, no effect of the VF test on IOP was found (global model fit R2 = 0.12), whether based on duration of the VF test (P = 0.18) or the MD (P = 0.7) after adjustment for age, gender, CCT and history of glaucoma surgery. Similarly, there was no significant difference within different types of glaucoma, including open-angle glaucoma (P = 0.36), chronic angle closure glaucoma (P = 0.85) and OHT (P = 0.42). The subgroup of patients with an IOP elevation ≥2 mmHg had a significantly higher VF test duration (P = 0.002). CONCLUSION: VF testing does not influence IOP as measured with a non-contact tonometer.

Cataract and glaucoma combined surgery: XEN® gel stent versus nonpenetrating deep sclerectomy, a pilot study.

BACKGROUND: To compare the efficacy of phacoemulsification (PKE) combined with nonpenetrating deep sclerectomy (NPDS) with mitomycin C (MMC) versus XEN® gel stent with MMC. METHODS: In this nonrandomized, retrospective, comparative, single-center pilot study, 105 consecutive eyes of 75 patients with uncontrolled primary open-angle glaucoma (POAG) and cataract who underwent PKE combined with either XEN implantation (n = 47) or NPDS (n = 58) between May 2013 and November 2018 were included. The primary outcome was complete success at 9 months, which was defined as intraocular pressure (IOP) ≤18, 15 or 12 mmHg without treatment; qualified success was IOP ≤18, 15 or 12 mmHg with antiglaucoma medications. Secondary outcome measures included the number of antiglaucoma medications, visual acuity (VA), and postoperative adverse events. RESULTS: Using the 18 mmHg threshold, complete or qualified success was achieved in 69.6 and 89.1% in the PKE + XEN group, and 63.8 and 89.7% in the PKE + NPDS group (p = .54 and p = .93), respectively, at 9 months. The mean IOP decreased from 20.8 ± 6.8 mmHg to 16.2 ± 2.8 mmHg in the PKE + XEN group (p < .001, 18.9% mean drop), and from 21.5 ± 8.9 mmHg to 14.9 ± 3.9 mmHg in the PKE + NPDS group (p < .001, 25.6% mean drop). Best-corrected VA significantly improved (p < .001) in both groups. The mean number of antiglaucoma medications was significantly reduced from 2.66 ± 1.1 to 0.49 ± 1.0 in the PKE + XEN group (p < .001) and from 2.93 ± 0.9 to 0.69 ± 1.2 in the PKE + NPDS group (p < .001). CONCLUSIONS: The XEN stent combined with PKE seemed to be as effective and safe as PKE + NPDS at 9 months in this pilot study.

Autologous Serum Eye Drops versus Artificial Tear Drops for Dry Eye Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To compare the efficacy of autologous serum (AS) eye drops and artificial tears (AT) in dry eye disease (DED). METHODS: Five databases (PubMed, Science Direct, the Cochrane Library, the Chinese National Knowledge Infrastructure, and the Wanfang Database) were searched for randomized controlled trials (RCTs). Efficacy was evaluated in terms of the Ocular Surface Disease Index (OSDI), Schirmer I test, tear break-up time (TBUT), and fluorescein and rose bengal staining of ocular surface. The estimated effects of AS or AT were expressed as a proportion with the 95% confidence interval and plotted on a forest plot. RESULTS: Seven RCTs with 267 subjects were included in the meta-analysis. For most of the studies, subjects' age was around 50 years old, and the mostly treatment duration was within 8 weeks. The follow-up results showed that the OSDI after AS treatment was lower than that after the AT treatment: the mean difference (MD) was -10.75 (95% CI, -18.12; -3.39) points. There was no difference on the Schirmer I test after treatment between the two groups: the MD was 1.68 (95% CI, -0.65; 4.00) mm. The TBUT of the AS group was longer than that of the AT group, with an MD of 4.53 (95% CI, 2.02; 7.05) s. There was no statistically significant difference on fluorescein staining score of the ocular surface between the AS group and the AT group, the MD was -2.53 (95% CI, -6.08; 1.03) points. The rose bengal staining score of the AS group was slightly lower than that of the AT group after treatment: the MD was -0.78 (95% CI, -1.34; -0.22) points. CONCLUSION: AS could be an effective treatment for DED, improving OSDI, TBUT, and rose bengal staining score. Further RCTs with large samples and long-term follow-up are still needed to determine the exact role of AS in the management of DED.

Chronic dry eye induced corneal hypersensitivity, neuroinflammatory responses, and synaptic plasticity in the mouse trigeminal brainstem.

BACKGROUND: Dry eye disease (DED) is a multifactorial disease associated with ocular surface inflammation, pain, and nerve abnormalities. We studied the peripheral and central neuroinflammatory responses that occur during persistent DED using molecular, cellular, behavioral, and electrophysiological approaches. METHODS: A mouse model of DED was obtained by unilateral excision of the extraorbital lachrymal gland (ELG) and Harderian gland (HG) of adult female C57BL/6 mice. In vivo tests were conducted at 7, 14, and 21 days (d) after surgery. Tear production was measured by a phenol red test and corneal alterations and inflammation were assessed by fluorescein staining and in vivo confocal microscopy. Corneal nerve morphology was evaluated by nerve staining. Mechanical corneal sensitivity was monitored using von Frey filaments. Multi-unit extracellular recording of ciliary nerve fiber activity was used to monitor spontaneous corneal nerve activity. RT-qPCR and immunostaining were used to determine RNA and protein levels at d21. RESULTS: We observed a marked reduction of tear production and the development of corneal inflammation at d7, d14, and d21 post-surgery in DED animals. Chronic DE induced a reduction of intraepithelial corneal nerve terminals. Behavioral and electrophysiological studies showed that the DED animals developed time-dependent mechanical corneal hypersensitivity accompanied by increased spontaneous ciliary nerve fiber electrical activity. Consistent with these findings, DED mice exhibited central presynaptic plasticity, demonstrated by a higher Piccolo immunoreactivity in the ipsilateral trigeminal brainstem sensory complex (TBSC). At d21 post-surgery, mRNA levels of pro-inflammatory (IL-6 and IL-1ß), astrocyte (GFAP), and oxidative (iNOS2 and NOX4) markers increased significantly in the ipsilateral trigeminal ganglion (TG). This correlated with an increase in Iba1, GFAP, and ATF3 immunostaining in the ipsilateral TG of DED animals. Furthermore, pro-inflammatory cytokines (IL-6, TNFα, IL-1ß, and CCL2), iNOS2, neuronal (ATF3 and FOS), and microglial (CD68 and Itgam) markers were also upregulated in the TBSC of DED animals at d21, along with increased immunoreactivity against GFAP and Iba1. CONCLUSIONS: Overall, these data highlight peripheral sensitization and neuroinflammatory responses that participate in the development and maintenance of dry eye-related pain. This model may be useful to identify new analgesic molecules to alleviate ocular pain.

Long term effect of phacoemulsification on intraocular pressure in patients with medically controlled primary open-angle glaucoma.

BACKGROUND: The effect of cataract surgery on IOP in patients with primary open-angle glaucoma (POAG) is a subject of debate. We investigated the effect of cataract surgery by phacoemulsification on intraocular pressure (IOP) in patients with medically POAG . METHODS: Seventy eyes of 40 POAG patients undergoing cataract surgery by phacoemulsification were retrospectively evaluated. All patients had their POAG medically controlled without prior glaucoma surgery. Baseline demographics and clinical characteristics were recorded. IOP and the number of glaucoma medications were evaluated before and for 1 year after cataract surgery. We analyzed IOP variations from baseline with a Student t-test for a paired sample. We used a Pearson correlation coefficient and linear regression to study the relation between IOP change from baseline and preoperative characteristics. RESULTS: One year after phacoemulsification, IOP decreased by a mean 1.15 ± 3 mmHg (6.8 ± 18.1%) (P = 0.01) and the number of glaucoma medications remained unchanged with a difference of - 0.1 ± 0.43 (P = 0.09). Higher preoperative IOP was associated with a greater IOP decrease after 1 year of follow-up (P < 0.001). One and 7 days after cataract surgery, 12.9 and 4.2% of the eyes had IOP spikes > 30 mmHg, respectively. One year after cataract surgery, 75.7% of the POAG eyes maintained the same number of glaucoma medications while 17.1% had a decrease and 7.2% of the eyes required adding glaucoma medications. CONCLUSION: Cataract surgery by phacoemulsification in eyes with medically controlled POAG resulted at 1 year in a very small IOP decrease without a change in the number of glaucoma medications. A drop in IOP should not be expected after performing phacoemulsification alone in POAG patients.

Changes in choroidal thickness and optic nerve head morphology after filtering surgery: nonpenetrating deep sclerectomy versus trabeculectomy.

BACKGROUND: The purpose of this study was to evaluate the changes in choroidal thickness and lamina cribrosa position after nonpenetrating deep sclerectomy (NPDS) and trabeculectomy. METHODS: Twenty-three eyes with glaucoma that required filtering surgery were included (12 NDPS and 11 trabeculectomies) in this prospective observational study. OCT-enhanced depth imaging (OCT-EDI) was used to measure choroidal thickness, prelaminar tissue thickness and lamina cribrosa position before and 7 days and 1 month after surgery. All results are shown as median (interquartile range values). RESULTS: Intraocular pressure (IOP) was significantly lower 1 week after surgery than at baseline (7 (6/10) mmHg vs. 21 (18/26) mmHg; p < 0.001) with a mean 64% decrease. IOP remained significantly lower at 1 month with a 55% mean decrease as compared to baseline (10 (8/12) mmHg; p < 0.001). One week after surgery, the subfoveolar choroidal thickness (SFCT) significantly increased (372 (306/523) µm vs. 317 (227/413) µm; p = 0.04) and the prelaminar tissue (PLT) was significantly thicker (269 (162/360) µm vs. 138 (87/268) µm; p = 0.02) as compared to preoperative measurements. These changes were not statistically significant at one month. There were no differences concerning these parameters between the NPDS and trabeculectomy groups. During the first week, the SFCT increase was correlated with IOP reduction (r = - 0.41; p = 0.04). CONCLUSIONS: OCT-EDI allowed the visualization of structural changes at the level of the optic nerve and choroidal vascularization during acute IOP changes. No difference was observed between NPDS and trabeculectomy concerning these structural modifications.

Expression of cytokines in aqueous humor from fungal keratitis patients.

BACKGROUND: Although a series of reports on corneal fungal infection have been published, studies on pathogenic mechanisms and inflammation-associated cytokines remain limited. In this study, aqueous humor samples from fungal keratitis patients were collected to examine cytokine patterns and cellular profile for the pathogenesis of fungal keratitis. METHODS: The aqueous humor samples were collected from ten patients with advanced stage fungal keratitis. Eight aqueous humor samples from patients with keratoconus or corneal dystrophy were taken as control. Approximately 100 µl to 300 µl of aqueous humor in each case were obtained for examination. The aqueous humor samples were centrifuged and the cells were stained and examined under optical microscope. Bacterial and fungal cultures were performed on the aqueous humor and corneal buttons of all patients. Cytokines related to inflammation including IL-1ß, IL-6, IL-8, IL-10, TNF-α, and IFN-γ were examined using multiplex bead-based Luminex liquid protein array systems. RESULTS: Fungus infection was confirmed in these ten patients by smear stains and/or fungal cultures. Bacterial and fungal cultures revealed negative results in all aqueous humor specimens. Polymorphonuclear leukocytes were the predominant infiltrating cells in the aqueous humor of fungal keratitis. At the advanced stages of fungal keratitis, the levels of IL-1ß, IL-6, IL-8, and IFN-γ in the aqueous humor were significantly increased when compared with control (p<0.01). The levels of IL-10 and TNF-α also showed an ascending trend but with no statistical significance. CONCLUSIONS: High concentration of IL-1ß, IL-6, IL-8, and IFN-γ in the aqueous humor was associated with fungal keratitis.

Proinflammatory Markers, Chemokines, and Enkephalin in Patients Suffering from Dry Eye Disease.

Dry eye symptoms are among the leading complaints in ophthalmology. Dry eye disease (DED) is associated with significant pain affecting quality of life. Cellular and molecular mechanisms underlying ocular pain associated with DED are not fully understood. In this study, we investigated the ocular surface of patients with DED using in vivo confocal microscopy (IVCM) to quantify corneal nerve density and its relation with corneal inflammation. Gene expression of the proinflammatory markers HLA-DR, IL-6, CXCL12, and CCL2 and the receptors CXCR4 and CCR2, as well as PENK (enkephalin precursor), was therefore quantified in conjunctival impression cytology specimens. Thirty-two patients with DED and 15 age-matched controls were included. Subbasal nerve density was significantly lower in DED patients compared to controls. IVCM analysis revealed that DED patients had a significantly higher corneal dendritic cell density compared to controls. Conjunctival impression cytology analysis revealed that HLA-DR, IL-6, CXCR4, and CCL2/CCR2 mRNA levels were significantly increased in DED patients compared to controls, whereas PENK mRNA levels were significantly decreased. Similar results were obtained in vitro on immortalized human conjunctiva-derived epithelial cells challenged with osmotic stress that mimics the DED condition. These results demonstrate that proinflammatory molecules and endogenous enkephalin have opposite gene regulation during DED.

Increased corneal sub-basal nerve density in patients with Sjögren syndrome treated with topical cyclosporine A.

BACKGROUND: To evaluate quantitative and qualitative changes in sub-basal corneal nerves (SBN) via in vivo confocal microscopy in patients with Sjögren syndrome dry eye (SSDE) treated with topical cyclosporine A (CsA). DESIGN: Prospective, observational, non-randomized study. PARTICIPANTS: Thirty eyes of 30 patients with SSDE refractory to conventional treatment treated with CsA 0.05% twice daily for 6 months. Fifteen eyes of 15 healthy, age and gender matched, volunteers constituted the control group at baseline. METHODS: A clinical evaluation of dry eye, corneal sensation using Cochet-Bonnet esthesiometry and in vivo confocal microscopy analysis of the central cornea were performed prospectively at baseline for all patients, and after 6 months of treatment with CsA. MAIN OUTCOME MEASURES: Density, number, reflectivity and tortuosity of SBN, dendritic cell (DC) density, esthesiometry, and dry eye signs and symptoms. RESULTS: Topical CsA 0.05% improved clinical signs and symptoms, and increased corneal sensitivity. Following treatment, SBN density was significantly increased (P < 0.0001) associated with a decreased in DC density (P < 0.0001). The increase in SBN density after treatment was positively correlated with baseline SBN density (R2  = 0.33; P = 0.0008) and negatively correlated with baseline Ocular Surface Disease Index (R2  = 0.28; P = 0.002), Oxford score (R2  = 0.31; P = 0.002), and DC density (R2  = 0.37; P = 0.0003). CONCLUSIONS: Topical CsA led to an increase in corneal SBN density, improving clinical signs and symptoms of SSDE. Our results also suggest an improved response to treatment in patients with less initial nerve damage.

[Epidemiologic study of tear film lipid layer thickness measurement in the population of Taishitun Community in Beijing].

Objective: To investigate the distribution of tear film lipid layer thickness (LLT) and the relationship between symptoms and signs of dry eye and tear film LLT in the population of Taishitun Community in Beijing. Methods: A cross-sectional study. From May 2016 to August 2016, three streets of Taishitun Community were randomly selected as survey districts and 540 persons were taken as investigation subjects. Every participant completed 6 items of dry eye examinations as follows: questionnaire (Ocular Surface Disease Index, OSDI), measurement of tear film LLT, tear film break-up time (TBUT), corneal and conjunctival staining, SchirmerⅠtest and the infrared meibomian photography. According to their age, all participants were divided into four groups: junior group (<18 years old), youth group (18 to 40 years old), middle-aged group (41 to 59 years old) and the elderly group (over 60 years old). With the OSDI criteria, no dry eye symptom group (score, <12 points), mild to moderate dry eye symptom group (score, 12 to 32) and severe dry eye symptom group (score, 33-100) were included. With the statistical methods of variance analysis and multivariate Logistic regression analysis, distribution of the variables of LLT and the relationship between dry eye symptoms and LLT were studied. Results: A total of 473 residents finally participated in this study, and the response ratio was 87.6%. The values of LLT were normally distributed. The average LLT was (59.87±18.50) nm [(60.16±19.15) nm in males and (59.67±18.57) nm in females], and the comparison of LLT with different genders was not statistically significant (t=0.198, P=0.843). The tear film LLT of four different age groups had statistical significance (F=15.092, P<0.05), and increased with age [(56.10±18.33) nm in the junior group, (54.60±16.29) nm in the youth group, (60.61±19.18) nm in the middle-aged group and (73.25±14.58) nm in the elderly group]. The LLT was inversely proportional to the severity of dry eye symptoms. With a thinner LLT, the symptoms of the subjects turned severe. In the elderly with different degrees of symptoms, the LLT was significantly different (F=0.019, P<0.05), while in the youth and middle-aged groups with different degrees of symptoms, the LLT was not significantly different (F=0.096, P>0.05. F=0.538, P>0.05). In the OSDI symptom questionnaire, only blurred vision and decreased visual acuity were related to the tear film LLT (P<0.05). There was no significant correlation between the TBUT, SchirmerⅠtest result, meibomian gland loss rate and the tear film LLT (P>0.05). Conclusions: In Taishitun Community of Beijing, the values of tear film LLT had a normal distribution. The LLT was positively correlated with age, but inversely correlated with the severity of the symptoms of dry eye. There was no significant correlation between the LLT and the TBUT, SchirmerⅠtest result and meibomian gland loss rate.(Chin J Ophthalmol, 2017, 53: 495-501).

[Study on the evaluation of pterygium activity with in vivo confocal microscopy].

Objective: To observe the characteristics of pterygium with in vivo confocal microscopy (IVCM) and understand pterygium activity with the density of inflammatory cells, formation of new blood vessels, and the number of activated keratocytes within the stroma. Methods: A prospective case-controlled study. Thirty-six pterygia from 28 patients were analyzed in this study. A pterygium activity score was obtained by summing four scores of ocular discomfort, pterygium hyperemia, keratitis, and the presence of Fuchs patches. Among them, the low activity of pterygium (PAS score less than 3 points) appeared in 12 eyes and high activity of pterygium (PAS score ≥ 4 points) in 24 eyes. All Patients underwent pterygium IVCM quantitative analysis by observing the boundaries between the pterygium and the adjacent cornea, the density of goblet cells and dendritiform inflammatory cells and Fuchs patches. The correlation of pterygium activity between IVCM and PAS with slit lamp was analyzed with Spearman correlation analysis. Results: The presence of inflammatory cells, numerous blood vessels, and irregular boundary between the cornea and the pterygium with infiltration of hyper-reflective cells in the adjacent corneal epithelium were signs observed with IVCM associated with pterygium activity. With IVCM technique, epithelial cells, goblet cells, and dendritiform inflammatory cells of various sizes were observed within the pterygium epithelium.The active (PAS ≥4) pterygium showed irregular boundaries between the pterygium and the adjacent cornea (score, 0.84±0.51) comparing with inactive subjects (score 0.23±0.12, t=2.68, P=0.009). Fuchs patches were observed as islets of hyper-reflective polygonal cells in front of the pterygium head with blurred boundary. The score (0.75±0.25) in active group showed significant changes as compared with normal subjects (0.23±0.12, t=3.79, P=0.001). The score of dendritiform inflammatory cells, activated keratocytes, and goblet cells in active group were 2.75±0.76, 1.92±0.68, and 2.08±0.42, which were significantly higher than those in inactive group (1.25±0.55, 0.50±0.25, 1.15±0.32, P=0.035, 0.030, <0.01). There was significant positive correlation between IVCM activity and traditional slit lamp PAS. Conclusion: Quantitative analysis of dendritiform inflammatory cells, vascular proliferation and activated keratocytes of pterygium by IVCM may be a reliable evaluation method to evaluate the activity of pterygium.(Chin J Ophthalmol, 2016, 52: 755-763).