Therapeutic Aqueous Humor Concentrations of Latanoprost Attained in Rats by Administration in a Very-High-Molecular-Weight Hyaluronic Acid Eye Drop.

The temporal change in concentration of a novel medicine, Latanoprost (LP), was evaluated in the aqueous humor of rats (6-8-week-old Jcl:Wister rats) when delivered in a very-high-molecular-weight hyaluronic acid (vHiHA) eye drop. Animals were randomly assigned to three treatment groups (LP + vHiHA (LPvHiHA), commercial LP (cLP), and diluted LP (dLP)) and after instilling the eye drops, the aqueous humor (AH) was collected at 0.5, 1, 2, 4, and 6 h to measure the LP concentration using an enzyme-linked immunosorbent assay (ELISA). Although the LP concentration in the LPvHiHA eye drop formulation was 3.57 times lower than in the commercial eye drops used (cLP), the LP concentration in the AH following LPvHiHA administration reached a value close to that of cLP. The cLP was diluted to the same concentration of LP as in the LPvHiHA eye drops for the dLP group, but the LP concentration in the AH of these animals was lower than that of the LPvHiHA rats at all time points. The higher LP concentration in the AH of the LPvHiHA rats suggests that vHiHA may aid the transport of LP across the ocular surface epithelium.

Deep learning model for extensive smartphone-based diagnosis and triage of cataracts and multiple corneal diseases.

AIM: To develop an artificial intelligence (AI) algorithm that diagnoses cataracts/corneal diseases from multiple conditions using smartphone images. METHODS: This study included 6442 images that were captured using a slit-lamp microscope (6106 images) and smartphone (336 images). An AI algorithm was developed based on slit-lamp images to differentiate 36 major diseases (cataracts and corneal diseases) into 9 categories. To validate the AI model, smartphone images were used for the testing dataset. We evaluated AI performance that included sensitivity, specificity and receiver operating characteristic (ROC) curve for the diagnosis and triage of the diseases. RESULTS: The AI algorithm achieved an area under the ROC curve of 0.998 (95% CI, 0.992 to 0.999) for normal eyes, 0.986 (95% CI, 0.978 to 0.997) for infectious keratitis, 0.960 (95% CI, 0.925 to 0.994) for immunological keratitis, 0.987 (95% CI, 0.978 to 0.996) for cornea scars, 0.997 (95% CI, 0.992 to 1.000) for ocular surface tumours, 0.993 (95% CI, 0.984 to 1.000) for corneal deposits, 1.000 (95% CI, 1.000 to 1.000) for acute angle-closure glaucoma, 0.992 (95% CI, 0.985 to 0.999) for cataracts and 0.993 (95% CI, 0.985 to 1.000) for bullous keratopathy. The triage of referral suggestion using the smartphone images exhibited high performance, in which the sensitivity and specificity were 1.00 (95% CI, 0.478 to 1.00) and 1.00 (95% CI, 0.976 to 1.000) for 'urgent', 0.867 (95% CI, 0.683 to 0.962) and 1.00 (95% CI, 0.971 to 1.000) for 'semi-urgent', 0.853 (95% CI, 0.689 to 0.950) and 0.983 (95% CI, 0.942 to 0.998) for 'routine' and 1.00 (95% CI, 0.958 to 1.00) and 0.896 (95% CI, 0.797 to 0.957) for 'observation', respectively. CONCLUSIONS: The AI system achieved promising performance in the diagnosis of cataracts and corneal diseases.

Three-Dimensional Assessment of Descemet Membrane Reflectivity by Optical Coherence Tomography in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: This study aimed to evaluate Descemet membrane reflectivity using anterior segment optical coherence tomography (AS-OCT) in eyes with Fuchs endothelial corneal dystrophy (FECD). METHODS: We retrospectively assessed 144 eyes of 88 consecutive participants (41 FECD, 15 pseudophakic bullous keratopathies [BKs], and 32 healthy controls, 63.5 ± 16.5 years). FECD was graded 0 to 3 based on the guttae areas using specular microscopy. The sum of AS-OCT reflectivity of the 3-dimensional volume from 10 µm thickness from the endothelial surface of the cornea and residual stromal area was calculated as D sum (endo) and D sum (stroma) in the central area of 3- and 6-mm diameters, respectively. The D ES ratio was defined as the ratio of D sum (endo) to D sum (stroma). The percentage of the guttae area in the specular images was calculated using MATLAB. D sum (endo) and D ES ratio were compared among FECD, BK, and healthy controls. RESULTS: D sum (endo) in FECD grade 3 was significantly higher than that in healthy control eyes, FECD patients with mild and moderate guttae, and BK (all P ≤ 0.040). The D ES ratio in FECD patients with mild to severe guttae (grade 1-3) was significantly higher than that in healthy control eyes and BK (all P ≤ 0.035). The percentage of the guttae area was significantly correlated with D sum (endo) (R = 0.488, P < 0.001 for 3 mm, R = 0.512, P < 0.001 for 6 mm) and D ES ratio (R = 0.450, P < 0.001 for 3 mm, R = 0.588, P < 0.001 for 6 mm). CONCLUSIONS: Descemet membrane reflectivity in AS-OCT can be objective biomarkers for assessing guttae and FECD severity from early to end-stage FECD.

Incidence and Clinical Features of Immunologic Rejection After Deep Anterior Lamellar Keratoplasty.

PURPOSE: The aim of this study was to investigate the incidence and clinical features of immunologic rejection after deep anterior lamellar keratoplasty (DALK). METHODS: This study included 411 patients (464 eyes, median age [interquartile range; IQR] 55.8 years [36.1-69.5]) who underwent DALK at Tokyo Dental College between June 1997 and 2021. Of 411 patients, 24 (24 eyes [5.2%], 51.9 years [IQR 31.6-65.4]) developed immunologic rejection. We characterized the clinical features, risk factors associated with immunologic rejection, and prognosis. RESULTS: The interval between DALK and immunologic rejection was 14.5 (range, 5-78) months. Immunologic rejection occurred after cessation/reduction of topical steroid in 9 (47.4%) and suture removal in 4 eyes (21.1%). The postoperative duration of topical steroid use in eyes with immunologic rejection was significantly shorter (10.0 months, [IQR 6.0-14.0]) than those without immunologic rejection (28.3 [IQR 15.8-42.7], P = 0.001). Immunologic rejection manifested as stromal edema in 19 (100.0%), ciliary hyperemia in 17 (89.5%), keratic precipitates in 13 (68.4%), epithelial edema in 13 (68.4%), infiltration in 9 (47.4%), corneal opacity in 4 (21.1%), and Descemet membrane detachment in 2 eyes (10.5%). After treatment, corneal clarity was restored in 17 eyes (89.5%); however, immunologic rejection led to corneal endothelial decompensation in 2 eyes (10.5%). Endothelial cell density decreased from 1795.7 ± 722.6 to 1651.6 ± 655.6 cells/mm2 after immunologic rejection (P = 0.074). CONCLUSIONS: Post-DALK immunologic rejection was associated with specific clinical triggers such as reduction/cessation of topical steroids or suture removal.

Risk Factors for Recurrence in the Treatment of Recurrent Pterygium.

PURPOSE: The aim of this study was to identify the postoperative recurrence rate of recurrent pterygium and to evaluate risk factors for the recurrence. METHODS: This study was a retrospective interventional nonrandomized consecutive case series. In this single-center study, 119 eyes of patients with recurrent pterygium who underwent surgery with a follow-up period of >12 months after the surgery were analyzed. The clinical characteristics of pterygium were classified according to the length of corneal involvement and Tan grade. The main outcome was the recurrence rate. The secondary outcome was the risk factors for recurrence. RESULTS: The mean follow-up period was 42 ± 28.6 months. Recurrence was observed in 15 patients (12.6%). The average postoperative recurrence period was 7.7 ± 6.7 months. Twelve patients experienced a recurrence within 12 months. Eyes with recurrence had a significantly greater length of corneal involvement (2.47 ± 0.72 mm) and number of previous surgery (1.9 ± 1.3) than those without (1.97 ± 0.74 mm, and 1.3 ± 0.7, both P = 0.04). Multivariate analysis showed that recurrence was significantly associated with the length of corneal involvement (odds ratio [OR] 2.38, 95% confidence interval [CI], 1.02-5.57, P = 0.05) and the number of previous surgeries (OR: 1.91, 95% CI, 1.03-3.58, P = 0.04) but not with sex (OR: 3.71, 95% CI, 0.90-15.2, P = 0.07), age (OR: 0.99, 95% CI, 0.94-1.04, P = 0.59), and use of mitomycin C (OR: 0.31, 95% CI, 0.07-1.21, P = 0.09). CONCLUSIONS: The postoperative recurrence rate of recurrent pterygium was 12.6%. The preoperative length of corneal involvement and number of previous pterygium surgeries were significantly correlated with recurrence. Male sex and nonuse of mitomycin C tended to correlate with recurrence.

Systematic Review of the Diagnostic Criteria and Severity Classification for Fuchs Endothelial Corneal Dystrophy.

PURPOSE: There are no defined diagnostic criteria and severity classification for Fuchs endothelial corneal dystrophy (FECD), which are required for objective standardized assessments. Therefore, we performed a systematic literature review of the current diagnosis and severity classification of FECD. METHODS: We searched the Ovid MEDLINE and Web of Science databases for studies published until January 13, 2021. We excluded review articles, conference abstracts, editorials, case reports with <5 patients, and letters. RESULTS: Among 468 articles identified, we excluded 173 and 165 articles in the first and second screenings, respectively. Among the 130 included articles, 61 (47%) and 99 (76%) mentioned the diagnostic criteria for FECD and described its severity classification, respectively. Regarding diagnosis, slitlamp microscope alone was the most frequently used device in 31 (51%) of 61 articles. Regarding diagnostic findings, corneal guttae alone was the most common parameter [adopted in 23 articles (38%)]. Regarding severity classification, slitlamp microscopes were used in 88 articles (89%). The original or modified Krachmer grading scale was used in 77 articles (78%), followed by Adami's classification in six (6%). Specular microscopes or Scheimpflug tomography were used in four articles (4%) and anterior segment optical coherence tomography in one (1%). CONCLUSIONS: FECD is globally diagnosed by the corneal guttae using slitlamp examination, and its severity is predominantly determined by the original or modified Krachmer grading scale. Objective severity grading using Scheimpflug or anterior segment optical coherence tomography can be applied in the future innovative therapies such as cell injection therapy or novel small molecules.

Artificial intelligence to estimate the tear film breakup time and diagnose dry eye disease.

The use of artificial intelligence (AI) in the diagnosis of dry eye disease (DED) remains limited due to the lack of standardized image formats and analysis models. To overcome these issues, we used the Smart Eye Camera (SEC), a video-recordable slit-lamp device, and collected videos of the anterior segment of the eye. This study aimed to evaluate the accuracy of the AI algorithm in estimating the tear film breakup time and apply this model for the diagnosis of DED according to the Asia Dry Eye Society (ADES) DED diagnostic criteria. Using the retrospectively corrected DED videos of 158 eyes from 79 patients, 22,172 frames were annotated by the DED specialist to label whether or not the frame had breakup. The AI algorithm was developed using the training dataset and machine learning. The DED criteria of the ADES was used to determine the diagnostic performance. The accuracy of tear film breakup time estimation was 0.789 (95% confidence interval (CI) 0.769-0.809), and the area under the receiver operating characteristic curve of this AI model was 0.877 (95% CI 0.861-0.893). The sensitivity and specificity of this AI model for the diagnosis of DED was 0.778 (95% CI 0.572-0.912) and 0.857 (95% CI 0.564-0.866), respectively. We successfully developed a novel AI-based diagnostic model for DED. Our diagnostic model has the potential to enable ophthalmology examination outside hospitals and clinics.

Corneal higher-order aberrations in corneal endothelial decompensation secondary to obstetric forceps injury.

Forceps corneal injuries during infant delivery cause Descemet membrane (DM) breaks, that cause corneal astigmatism and corneal endothelial decompensation. The aim of this study is to characterise corneal higher-order aberrations (HOAs) and corneal topographic patterns in corneal endothelial decompensation due to obstetric forceps injury. This retrospective study included 23 eyes of 21 patients (54.0 ± 9.0 years old) with forceps corneal injury, and 18 healthy controls. HOAs and coma aberrations were significantly larger in forceps injury (1.05 [0.76-1.98] µm, and 0.83 [0.58-1.69], respectively) than in healthy controls (0.10 [0.08-0.11], and 0.06 [0.05-0.07], respectively, both P < 0.0001). Patient visual acuity was positively correlated with coma aberration (rs = 0.482, P = 0.023). The most common topographic patterns were those of protrusion and regular astigmatism (both, six eyes, 26.1%), followed by asymmetric (five eyes, 21.7%), and flattening (four eyes, 17.4%). These results indicate that increased corneal HOAs are associated with decreased visual acuity in corneal endothelial decompensation with DM breaks and corneal topography exhibits various patterns in forceps injury.

Morphological alterations in corneal nerves of patients with dry eye and associated biomarkers.

The purposes of the present study were to (1) identify the relationship between dry eye symptoms and morphological changes in corneal subbasal nerves/ocular surfaces, and (2) discover tear film biomarkers indicating morphological changes in the subbasal nerves. This was a prospective cross-sectional study conducted between October and November 2017. Adults with dry eye disease (DED, n = 43) and healthy eyes (n = 16) were evaluated based on their subjective symptoms and ophthalmological findings. Corneal subbasal nerves were observed using confocal laser scanning microscopy. Nerve lengths, densities, branch numbers, and nerve fiber tortuosity were analyzed using ACCMetrics and CCMetrics image analysis systems; tear proteins were quantified by mass spectroscopy. Compared with the control group, the DED group had significantly lower tear breakup times (TBUT) and pain tolerance capacity, and significantly higher corneal nerve branch density (CNBD) and corneal nerve total branch density (CTBD). CNBD and CTBD showed significant negative correlations with TBUT. Six biomarkers (cystatin-S, immunoglobulin kappa constant, neutrophil gelatinase-associated lipocalin, profilin-1, protein S100-A8, and protein S100-A9) showed significant positive correlations with CNBD and CTBD. The significantly higher CNBD and CTBD in the DED group suggests that DED is associated with morphological alterations in corneal nerves. The correlation of TBUT with CNBD and CTBD further supports this inference. Six candidate biomarkers that correlate with morphological changes were identified. Thus, morphological changes in corneal nerves are a hallmark of DED, and confocal microscopy may help in the diagnosis and treatment of dry eyes.

Diagnostic Ability of a Smartphone App for Dry Eye Disease: Protocol for a Multicenter, Open-Label, Prospective, and Cross-sectional Study.

BACKGROUND: Dry eye disease (DED) is one of the most common ocular surface diseases. Numerous patients with DED remain undiagnosed and inadequately treated, experiencing various subjective symptoms and a decrease in quality of life and work productivity. A mobile health smartphone app, namely, the DEA01, has been developed as a noninvasive, noncontact, and remote screening device, in the context of an ongoing paradigm shift in the health care system, to facilitate a diagnosis of DED. OBJECTIVE: This study aimed to evaluate the capabilities of the DEA01 smartphone app to facilitate a DED diagnosis. METHODS: In this multicenter, open-label, prospective, and cross-sectional study, the test method will involve using the DEA01 smartphone app to collect and evaluate DED symptoms, based on the Japanese version of the Ocular Surface Disease Index (J-OSDI), and to measure the maximum blink interval (MBI). The standard method will then involve a paper-based J-OSDI evaluation of subjective symptoms of DED and tear film breakup time (TFBUT) measurement in an in-person encounter. We will allocate 220 patients to DED and non-DED groups, based on the standard method. The primary outcome will be the sensitivity and specificity of the DED diagnosis according to the test method. Secondary outcomes will be the validity and reliability of the test method. The concordance rate, positive and negative predictive values, and the likelihood ratio between the test and standard methods will be assessed. The area under the curve of the test method will be evaluated using a receiver operating characteristic curve. The internal consistency of the app-based J-OSDI and the correlation between the app-based J-OSDI and paper-based J-OSDI will be assessed. A DED diagnosis cutoff value for the app-based MBI will be determined using a receiver operating characteristic curve. The app-based MBI will be assessed to determine a correlation between a slit lamp-based MBI and TFBUT. Adverse events and DEA01 failure data will be collected. Operability and usability will be assessed using a 5-point Likert scale questionnaire. RESULTS: Patient enrollment will start in February 2023 and end in July 2023. The findings will be analyzed in August 2023, and the results will be reported from March 2024 onward. CONCLUSIONS: This study may have implications in identifying a noninvasive, noncontact route to facilitate a diagnosis of DED. The DEA01 may enable a comprehensive diagnostic evaluation within a telemedicine setting and facilitate early intervention for undiagnosed patients with DED confronting health care access barriers. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs032220524; https://jrct.niph.go.jp/latest-detail/jRCTs032220524. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/45218.

Etiology-Specific Comparison of the Long-Term Clinical Outcome of Repeat Deep Anterior Lamellar Keratoplasty for Optical Indications.

PURPOSE: The aim of this study was to evaluate the etiology-specific clinical outcomes and complications of repeat deep anterior lamellar keratoplasty (DALK) after failed DALK. METHODS: This retrospective case study included 32 eyes of 27 patients who underwent repeat DALK of 450 cases of DALK performed for optical indications between 1997 and 2013. The patients were divided into 4 etiology-specific subgroups (the corneal dystrophy, ocular surface disease, stromal scar, and others) or those with or without limbal stem cell deficiency (LSCD). The clinical outcomes evaluated were graft survival, best-corrected visual acuity, endothelial cell density, and complications. RESULTS: The mean postoperative follow-up duration was 69.6 ± 54.8 months. The 1-, 3-, and 5-year overall graft survival rate were 76.7%, 57.5%, and 38.8% respectively. The graft survival rate was the highest in the corneal dystrophy group ( P = 0.0014) and was significantly ( P = 0.0010) higher in eyes without LSCD than in eyes with LSCD. There were no significant differences in the graft survival rates between the previous and current DALK groups. The postoperative best-corrected visual acuity of all subjects improved significantly. The postoperative endothelial cell density did not decrease after repeat DALK. There were no significant differences in the incidence of complications between patients with and without LSCD, except the incidence of persistent epithelial defects. CONCLUSIONS: Repeat DALK had favorable outcomes in all etiology-specific groups, whereas eyes with LSCD required careful assessment of the ocular surface to avoid graft failure due to persistent epithelial defects.

Clinical Trial of Autologous Cultivated Limbal Epithelial Cell Sheet Transplantation for Patients with Limbal Stem Cell Deficiency.

PURPOSE: To confirm the efficacy and safety of Good Manufacturing Practice (GMP)-compliant autologous cultivated limbal epithelial cell sheets in government-controlled clinical trials that adhered to Good Clinical Practice stipulations for patients with unilateral limbal stem cell deficiency (LSCD). DESIGN: A prospective, multicenter, open-label, uncontrolled, single-arm clinical trial. PARTICIPANTS: Ten consecutive eyes of 10 patients with unilateral LSCD were followed for 2 years after surgery. Preoperative LSCD stage was IIB in 4 eyes and III in 6 eyes. METHODS: A limbal tissue biopsy was obtained from the healthy eye, after which limbal stem cells were dissociated and cultivated on temperature-responsive culture surfaces. All cell sheets were fabricated in a GMP-grade facility under established standard operating procedures. Cell sheets were evaluated using defined shipment criteria before transplantation, and only those that met the criteria were used. The cell sheet was transplanted onto each of the patients' diseased eye after removing the conjunctival scar tissue that covered the corneal surface. The severity of LSCD was determined according to a staging method agreed on by global consensus, with eyes evaluated as being in stages IA-C representing successful corneal epithelial reconstruction. Diagnosis and staging of LSCD were determined by the trial's Eligibility Judgment Committee and Effect Assessment Committee using slit-lamp photographs including fluorescein staining. Both committees comprised 2 or 3 third-party cornea specialists, who were provided with information anonymously and randomly. MAIN OUTCOME MEASURE: Corneal epithelial reconstruction rate was the primary end point. RESULTS: Corneal epithelial reconstruction was successful in 6 of 10 eyes (60%) 1 year postoperatively and was significantly higher than the 15% clinically significant efficacy rate achieved by allogeneic limbal transplantation. The reconstruction rate was 70% of eyes 2 years postoperatively. Additionally, improvements in visual acuity were noted in 50% and 60% of eyes at 1 and 2 years, respectively. No clinically significant transplantation-related adverse events were observed. CONCLUSIONS: The efficacy and safety of cultivated limbal epithelial cell sheet transplantation were thus confirmed, and the cell sheet, named "Nepic," is now approved as a cellular and tissue-based product in Japan. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Changes in corneal higher-order aberrations during treatment for infectious keratitis.

This study aimed to quantify the changes in corneal higher-order aberrations (HOAs) before and after treatment for infectious keratitis and verify the correlation between corneal HOAs and visual acuity. Corneal HOAs were analysed using swept-source anterior segment optical coherence tomography (AS-OCT). Ninety-eight eyes of 96 consecutive patients with infectious keratitis treated with topical eye drops were retrospectively evaluated. Corneal HOAs increased with the infection but decreased with infection resolution following antimicrobial treatment. Corneal HOAs became larger as the degree of corneal findings became more severe. The increase in HOAs of the total cornea was correlated with the decrease in visual acuity both before and after treatment (4 mm, ρ = 0.530 and 0.590; 6 mm, ρ = 0.479 and 0.567, respectively; all P < 0.0001). Furthermore, pretreatment HOA (anterior, 6 mm), pretreatment logMAR best spectacle-corrected visual acuity, and age were prognostic factors significantly associated with posttreatment visual acuity (ß = 0.31, P = 0.013; ß = 0.36, P < 0.0001; and ß = 0.35, P = 0.0007, respectively) (adjusted R2 = 0.474). These results indicate that corneal HOAs quantified using AS-OCT can be used as an objective index to evaluate corneal optical function during the treatment of infectious keratitis.

The predictability of graft thickness for Descemet's stripping automated endothelial keratoplasty using a mechanical microkeratome system.

Descemet's stripping automated endothelial keratoplasty (DSAEK) is used for treating corneal endothelial dysfunction, and the postoperative visual acuity outcome depends on the thickness of the graft. We created a simple nomogram using factors affecting the cutting thickness during graft preparation via a mechanical microkeratome system for DSAEK. This retrospective study was conducted from May 2018 through October 2022 and included donor eyes cut by automatic methods. We measured the graft thickness, cutting accuracy, and assessed ten variables with donor/cornea-related factors potentially affecting the cutting thickness. Subsequently, we created a simple nomogram. We analyzed 81 donor tissues, and the donor median age was 76 years. The mean central graft thickness was 122.2 µm, with 62% of the grafts that could be cut within the target central graft thickness range. Comparatively, donor corneas from those with cardiac diseases were cut deeper (P = 0.007). The developed nomogram provided a 83% probability of estimating the post-cutting graft thickness within 25 µm. Our nomogram, which considers cause of death, enables reproducible production of graft of a desired thickness. A detailed analysis of donor tissues, including the cause of donor death and the characteristics from pressurization to cutting, will enable more precise DSAEK graft preparation.

Quercetin improves lacrimal gland function through its anti-oxidant actions: Evidence from animal studies, and a pilot study in healthy human volunteers.

Anti-oxidant properties of polyphenols have been gaining medical attention as a preventive factor against aging and/or lifestyle diseases. In this study, we examined the anti-oxidant activity of quercetin improved tear function through its effects on the lacrimal gland in mice and humans. Six week-old diabetic mice, a model for decreased tear production, were fed for 12 weeks ad libitum with an experimental diet containing 0.5% quercetin. As a result, the tear volume was significantly improved compared to the control, despite no changes in body weight, food intake, lacrimal gland morphology or biochemical serum parameters. Moreover, significantly higher SOD-1 and SOD-2 protein levels were detected in the lacrimal glands of quercetin-treated mice by western blot. In addition, quercetin treatment of mouse corneal cell lines exposed to oxidative stress resulted in dose-dependent inhibition of ROS production and enhanced cell survival. Finally, we examined quercetin pharmacokinetics, specifically its presence in serum and tears subsequent to onion consumption in healthy volunteers, and found that the distribution of quercetin and its metabolite shifted from serum to tear following onion intake. An improvement in tear film stability also resulted following the intake by these healthy volunteers of a new, quercetin-rich onion cultivar ("Quergold") in powder form. These results suggested that quercetin improved tear function through its effects on the lacrimal gland in mice and humans.

Graft Size and Double Scroll Formation Rate in Descemet Membrane Endothelial Keratoplasty.

PURPOSE: This study aimed to evaluate the usefulness of intentional double scroll formation of donor Descemet membrane (DM) inside a glass tube inserter (the Fogla technique) in DM endothelial keratoplasty (DMEK) for controlled insertion and unfolding of grafts. METHODS: Eleven consecutive patients who underwent DMEK were included in this study. We sought to specify graft characteristics in which double scroll configuration was successfully formed using the Fogla technique. We compared donor age, graft size, surgical time, unfolding time, and visual outcomes between patients with and without double scroll configuration. The ability to form double scroll formation of DM grafts of various diameters and unfolding time of DM grafts was evaluated using total seven eye-bank eyes in ex vivo experiments. RESULTS: A double scroll configuration inside a glass tube was successfully obtained in six DMEK grafts (54.5%). When comparing clinical features between those with and without double scroll configuration, only graft size was significantly larger in those with double scroll configuration (7.9 ± 0.2 mm) than in those without (7.4 ± 0.4, P = 0.03). There were no significant differences in other features and clinical outcomes, although unfolding-time was shorter in eyes with double scroll configuration (4.6 ± 2.0 min) compared to those without (8.6 ± 8.1, P = 0.21). Ex vivo experiments showed that unfolding time was significantly shorter in double scroll configuration (2.71 ± 0.49 min) than in single scroll (5.02 ± 0.79, P = 0.01). CONCLUSIONS: A double scroll configuration within a glass tube can be obtained more frequently in larger DMEK grafts (8.0 mm in diameter), which may result in easier and faster DMEK procedures.

The Impact of Noncontact Tonometry and Icare Rebound Tonometry on Tear Stability and Dry Eye Clinical Practice.

The purpose of this study was to investigate the possible effects of the noncontact air puff tonometry (NCT) and Icare rebound tonometry (ICT) on the tear film stability by using the tear stability analysis system (TSAS) and dry eye parameters. Fifteen eyes from fifteen normal healthy subjects were investigated in this study. All subjects underwent TSAS surface regularity index (SRI) examinations, TBUT, and IOP measurements. The mean IOP results measured with NCT were 13.3 ± 1.86 mm Hg, and the mean IOP results measured with ICT were 15.88 ± 3.09 mm Hg (p > 0.05). The mean values of baseline, 5 min, and 10 min of the NCT-SRI and ICR-SRI were tested. There were statistically significant differences between NCT-Baseline SRI, NCT-5 min SRI, and NCT-10 min SRI values (p < 0.05). SRI values significantly increased after NCT. The mean values of the baseline, 5 min, and 10 min of the ICT-SRI were also assessed. There were no statistically significant differences between ICT-Baseline SRI, ICT-5 min SRI, and ICT-10 min SRI values (p > 0.05). The mean TBUT values exhibited a significant decrease at 1 min, 5 min, and 10 min compared with baseline values for the NCT and ICT (p < 0.01). NCT-TBUT and ICT-TBUT values were also compared with each other in the same time period. There were no statistically significant differences between NCT-Baseline and ICT-Baseline TBUT values (p > 0.05). In conclusion, intraocular pressure measurements in routine ophthalmology clinical practices by either NCT or ICT cause deterioration in the tear film stability which might affect tear stability testing when performed soon after IOP measurements. It is best to wait at least for 20−30 min after the IOP measurement before evaluating the tear film and the corneal surface or perform tonometry after the tear film-ocular surface evaluation tests.

Donor-Related Risk Factors for Graft Decompensation Following Descemet's Stripping Automated Endothelial Keratoplasty.

AIMS: To identify donor-related risk factors associated with graft endothelial failure and postoperative endothelial cell density (ECD) reduction after Descemet's stripping automated endothelial keratoplasty (DSAEK). METHODS: This was a single-center retrospective study conducted from July 2006-December 2016. We included 584 consecutive eyes (482 patients) that underwent DSAEK for the treatment of laser iridotomy-related bullous keratopathy (192 eyes), pseudophakic bullous keratopathy (137 eyes), regraft (96 eyes), Fuchs' endothelial corneal dystrophy (FECD; 59 eyes) and others (100 eyes). Twenty-three donor- and recipient-related risk factors potentially associated with graft failure and ECD reduction were assessed using Cox hazard models and linear mixed effect models. RESULTS: The median age of the patients was 73.5 years (male; 35.6%). After DSAEK, ECD decreased from 2,674 cells/mm2 (95% confidence interval [CI]; 2,646-2,701) to 1,132 (1,076-1,190) at 12 months and 904 (845-963) at 24 months (P < 0.001). Fifty-five eyes (9.4%) had graft endothelial failure without rejection. This failure was associated with donor pseudophakic lens status (hazard ratio [HR]; 2.67, CI; 1.50-4.76, P = 0.001) and preoperative endothelial folds (HR; 2.82, CI; 1.20-6.62, P = 0.02). The incidence of graft endothelial failure in non-FECD patients was significantly higher among those receiving donor grafts with a pseudophakic lens status and preoperative presence of endothelial folds (P < 0.001). Postoperative ECD loss was significantly greater in eyes with these risk factors compared to those without (P = 0.007). CONCLUSIONS: Pseudophakic status and/or presence of preoperative endothelial folds are the significant donor risk factors for endothelial failure in non-FECD patients.

Lost or fragmented bony septum of the optic canal facing the sphenoid sinus: a histological study using elderly donated cadavers.

PURPOSE: To histologically describe a direct contact (the so-called dehiscence) of the optic nerve (ON) and/or internal carotid artery (ICA) to the mucosa of posterior paranasal sinuses represented by the sphenoid sinus (SS). METHODS: Observations of histological sections of unilateral or bilateral skull bases (parasellar area and orbital apex) from 22 elderly cadavers were made. RESULTS: A bony septum was less than 300 µm between the SS and ICA and 200 µm between the SS and optic nerve. Parts of the septa were sometimes absent due to fragmentation and holes of the bony lamella (2/22 facing the ICA; 4 facing the ICA in combination with an absent bony septum facing the nerve). In these dehiscence sites, the SS submucosal tissue attached to a thick sheath (50-100 µm in thickness) enclosing the optic nerve and ophthalmic artery and/or the ICA adventitia (50-200 µm in thickness). The ICA sometimes contained a sclerotic plaque that attached to or even protruded into the SS. With or without dehiscence, the SS mucosa was always thin (50-100 µm in thickness) and accompanied no mononuclear cellular infiltration or tumor. CONCLUSIONS: A thin bony septum of the optic nerve or ICA had been notable as a danger point during surgery, but even a 0.05-mm-thick bone lamella might be an effective barrier against cellular infiltration or bacterial invasion from the SS. Fragmentation and holes of the bony lamella in 4 cadavers might allow cellular invasion to the optic nerve. Accordingly, unknown immunological cross talks might occur to cause demyelination.