Topical tacrolimus for high-risk corneal transplantation: a randomized, clinical trial.

BACKGROUND: The prevalence of rejection is 10-30% in penetrating keratoplasty (PKP) case, and the rate is higher in cases of high-risk patients. Although using topical corticosteroids is a standard method for management the rejection of post-PKP patients, it may not be sufficiently potent in high-risk patients. Topical administration of tacrolimus (TAC) may be effective in suppression rejection after corneal transplantation. This study aimed to investigate the efficacy and safety of topical TAC in high-risk PKP patients in Japan. METHODS: This study was a single centre, single-blinded, randomized controlled trial. Patients with a history of PKP, graft rejection, atopic dermatitis, or deep corneal neovascularisation who underwent PKP were enrolled. They were randomly assigned to receive 0.1% TAC ophthalmic suspension or artificial tear (AT) up to week 52 after surgery. All participants received 0.1% betamethasone up to week 13 after surgery then they received 0.1% fluorometholone up to week 52. The incidence of immunological rejection during the observation period was the main outcome measure in this study. RESULTS: Thirty patients were enrolled in this study, and 12 eyes in the TAC group and 13 eyes in the AT group completed the study, respectively. Five out of 30 patients discontinued participation after providing informed consent. No serious adverse effects were developed in patients who received 0.1% TAC ophthalmic suspension. No rejection episodes occurred in the TAC group, while one eye in the AT group had rejection. Graft clarity, best spectacle-corrected visual acuity, intraocular pressure, and corneal endothelial cell density were not significantly different between the TAC and AT groups. CONCLUSION: Our results demonstrated that good tolerability of 0.1% TAC ophthalmic suspension. However, we failed to demonstrate its efficacy in preventing immunological rejection in high-risk patients undergoing PKP. TRIAL REGISTRATION: This study was first registered in the University Hospital Medical Information Network (UMIN000029669, Date of registration: November 1, 2017). With the enforcement of the Clinical Trial Act in Japan, the study re-registered in the Japan Registry of Clinical Trials (jRCTs031180342, Date of registration: March 18, 2019).

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.

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.

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.

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.

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.

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.

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.

Clinical efficacy of diquafosol sodium 3% versus hyaluronic acid 0.1% in patients with dry eye disease after cataract surgery: a protocol for a single-centre, randomised controlled trial.

INTRODUCTION: The number of cataract surgeries, the most common ophthalmic surgery, is expected to increase due to ageing populations. Dry eye disease (DED) is a frequent side effect of cataract surgery, contributing to lower postoperative patient satisfaction and suboptimal quality of vision. It is unclear which eye-drops commonly used in these patients should be recommended for postoperative DED treatment. This study aims to compare the efficacy of topical administration of diquafosol sodium 3% vs hyaluronic acid 0.1% eye-drops in patients with DED after cataract surgery. METHODS AND ANALYSIS: The study is designed as a single-blind randomised controlled trial. The participants will be randomly (1:1) allocated to either the diquafosol sodium 3% topical administration group (n=21) or the hyaluronic acid 0.1% topical administration group (n=21). Each group will receive its assigned eye-drop intervention over a 12-week period. The primary outcome will be measured using the total score of the Japanese version of the Ocular Surface Disease Index during the visit 5 weeks postoperatively. Both groups will be followed up after their respective eye-drop application for 12 weeks according to the intervention regimens. Secondary outcome measures including meibomian gland function assessment, tear film break-up time, keratoconjunctival staining score, maximum blink interval and tear secretion volume using Schirmer's test I will be assessed at 1, 5, 9, 13 and 25 weeks postoperatively. ETHICS AND DISSEMINATION: This study has been approved by the Juntendo Hospital Certified Review Board, Tokyo, Japan (Approved protocol V.7.0 dated 7 May 2021. Approval number: J20-018) and has been registered with the Japan Registry of Clinical Trials. Written informed consent will be collected from every patient prior to study participation. The results of this trial will be presented at local and international meetings and submitted to peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER: jRCT1031210018.

Outcome of Lamellar Graft Patching for the Treatment of Noninfectious Corneal Perforations.

PURPOSE: The aims of this study were to evaluate the clinical outcome of lamellar graft patching used for treating noninfectious corneal perforations and to determine the clinical factors affecting tectonic integrity. METHODS: This retrospective study includes a total of 71 eyes of 67 patients who underwent lamellar graft patching for the treatment of corneal perforations due to persistent epithelial defects secondary to limbal stem cell deficiency (LSCD, 21 eyes; 29.6%), peripheral ulcerative keratitis (17 eyes; 23.9%), neurotrophic keratitis due to herpes simplex keratitis (HSK, 14 eyes; 19.7%), and other causes (19 eyes; 26.8%). We evaluated the tectonic integrity of the globe, visual outcomes, and postoperative complications. RESULTS: Tectonic integrity was achieved in 53 eyes (74.6%). The survival proportions of eyes that achieved clear grafts were 77.8% and 65.2% at 12 and 24 months, respectively. Graft failure was observed in 19 eyes (26.8%). The survival rate of tectonic integrity and eyes that finally achieved a clear graft was significantly worse in eyes with LSCD compared with those without ( P < 0.001). The logarithm of minimal angle resolution improved significantly from 1.79 ± 0.98 to 1.22 ± 0.87 at 12 months and 1.08 ± 0.81 at 24 months. Postoperative complications included cataract formation (32 eyes, 45.1%), intraocular pressure rise (23 eyes, 32.4%), recurrent perforations (15 eyes, 21.1%), infectious keratitis (14 eyes, 19.7%), recurrence of herpes simplex keratitis (7 eyes, 9.9%), and traumatic graft dehiscence (1 eye, 1.4%). CONCLUSIONS: Lamellar graft patching is an effective and safe surgical treatment for noninfectious corneal perforations; however, careful attention to severe complications is necessary, especially in eyes with LSCD.

Elevated Cytokine Levels in Aqueous Humor Are Associated with Peripheral Anterior Synechiae after Penetrating Keratoplasty.

Peripheral anterior synechiae (PAS) after corneal transplantation leads to refractory glaucoma and permanent loss of vision. However, the exact mechanism remains elusive. This study aimed to evaluate the association between cytokine levels in the aqueous humor (AqH) and the progression of PAS after penetrating keratoplasty (PKP). We measured 20 cytokine levels in AqH and assessed the correlation with PAS progression after PKP in 85 consecutive patients who underwent PKP. We also evaluated age-dependent alterations in PAS and cytokine levels in DBA2J mice. PAS developed in 38 (44.7%) of 85 eyes after PKP. The incidence of intraocular pressure increase after PKP was significantly greater in eyes with PAS (26.3%) than in those without PAS (2%, p = 0.0009). The PAS area at 12 months after PKP was significantly positively correlated with the preoperative levels of interleukin (IL)-6, interferon (IFN)-γ and monocyte chemotactic protein (MCP)-1 (p ≤ 0.049). In the DBA2J mice, an experimental glaucoma model that developed PAS at 50 weeks, the AqH levels of IL-2, IL-6, IL-10, IFN-γ, tumor necrosis factor-α, MCP-1 and granulocyte-macrophage colony-stimulating factor (GM-CSF) significantly increased at 50 weeks compared to 8 weeks (p ≤ 0.021). In conclusion, inflammatory alterations in the AqH microenvironment, such as high preoperative specific cytokine levels, can lead to PAS formation and glaucoma.

Trends in surgical procedures and indications for corneal transplantation over 27 years in a tertiary hospital in Japan.

PURPOSE: To characterize trends in procedures, and indications for corneal transplantation over 27 years in a single referral center in Japan. STUDY DESIGN: Retrospective study. METHODS: Data from a consecutive series of corneal transplant surgery cases performed from 1991 to 2017at Ichikawa General Hospital were collected. The surgical procedures, indications, and causes of corneal endothelial dysfunction were evaluated. RESULTS: Among 6,025 transplantations, a total of 3,991 cases underwent penetrating keratoplasty (PKP), 1009 underwent (deep) anterior lamellar keratoplasty, 746 underwent endothelial keratoplasty, and 309 underwent epithelial transplantation. Over that period the frequency of PKP decreased, whereas the frequency of lamellar keratoplasty increased. The four major surgical indications were bullous keratoplasty (BK 30.0%), regraft (24.2%), post-keratitis scars (17.1%), and keratoconus (11.4%). After dividing the study period into four time periods, we found that BK and regraft increased (from 20.3% to 34.5% and 18.2% to 31.1%, respectively), whereas post-keratitis scars and keratoconus decreased (from 26.0% to 9.5% and 14.1% to 7.2%, respectively) between the first and last period. Pseudophakic or aphakic BK were the major causes of corneal endothelial dysfunction until 2010. Cases of laser-iridotomy-induced BK peaked in 35 eyes (34.3% of BK) in 2000 and declined after 2013. Cases of Fuchs endothelial corneal dystrophy increased from 0 in 1991, to 15 eyes (18.5% of BK) in 2017. CONCLUSION: Lamellar keratoplasty has replaced PKP in our hospital. BK and regraft have increased, whereas post-keratitis scars and keratoconus have decreased. Laser-iridotomy-induced BK has decreased during the past decade, whereas Fuchs endothelial corneal dystrophy has increased.

Long-Term Outcome After Superficial Keratectomy of the Abnormal Epithelium for Partial Limbal Stem Cell Deficiency.

PURPOSE: To investigate the etiology and long-term surgical prognosis of the abnormal epithelium for partial limbal stem cell deficiency (LSCD), following superficial keratectomy DESIGN: Retrospective, interventional case series METHODS: This single-center, retrospective study was conducted to assess the prognosis of consecutive patients who underwent superficial keratectomy, with or without amniotic membrane transplantation (AMT), for the treatment of partial LSCD, from 2010 to 2019. We analyzed the etiologies of partial LSCD, surgical success rate, prognosis for recurrent cases, and the improvement in visual acuity. RESULTS: We included 40 patients (51 eyes) with partial LSCD. All eyes were in clinical stage II without dense fibrovascular tissue. Idiopathy was the most common etiology (39%), followed by multiple surgeries involving the corneoscleral limbus (19%). All eyes attained corneal reepithelialization and transparency. Furthermore, the visual acuity improved or remained unchanged postoperatively. We observed recurrence in 19 eyes (37%) with a mean follow-up period of 26.3 months. Despite no significant difference in the recurrence rates among different etiologies, postoperative delayed epithelialization and extensive limbal involvement were identified as risk factors for recurrence (P < .001 and P = .013, respectively). Repeat surgeries were performed in 16 eyes. The final success rate was 84%. CONCLUSIONS: Superficial keratectomy is useful for the treatment of partial LSCD of varied etiologies, with an expected improvement in visual acuity postoperatively. Although the procedure can be repeated and have a high success rate, there have been several cases of recurrence in the long-term postoperative course.

Atypical Granulomatosis with Polyangiitis Presenting with Meibomitis, Scleritis, Uveitis and Papillary Bladder Tumor: A Case Report and Literature Review.

Granulomatosis with polyangiitis (GPA) presents with a variety of systemic findings, sometimes with ocular findings initially, but is often difficult to diagnose at an early stage. An 85-year-old male had complaints of ocular dryness and redness and was diagnosed with meibomian gland dysfunction with meibomitis. Despite an initial treatment with topical steroid and antibiotics, the meibomitis did not improve and the left eye developed scleritis and iridocyclitis. The patient was administered topical mydriatics and oral steroids. During follow-up, the patient developed left hearing difficulty and reported a darker urine. Urinalysis revealed microscopic hematuria. A blood test showed an elevated erythrocyte sedimentation rate, positivity for perinuclear anti-neutorophil cytoplasmic antibody, and elevations in blood urea nitrogen and serum creatinine. Nasal mucosal biopsy showed a non-necrotizing granulomatous inflammation. Renal biopsy revealed focal glomerulosclerosis. Cystoscopy and bladder wash followed by a planned transurethral resection revealed atypical cells and apical papillary tumors which were resected. Iridocyclitis and scleritis responded well to oral prednisolone with 0.1% topical betamethasone and prednisolone ointment. The patient is tumor free with no recurrences 24 months after resection. GPA may present atypically with meibomian gland dysfunction without showing representative clinical findings. Early detection and treatment are essential for visual recovery.

Long-term outcomes of cultivated cell sheet transplantation for treating total limbal stem cell deficiency.

PURPOSE: This study was conducted to determine the long-term outcomes of cultivated cell sheet transplantation (CCST), and to clarify risk factors that affected the outcomes. METHODS: We retrospectively analyzed the medical charts and photographs of 246 consecutive surgeries (162 eyes from 139 patients) that used CCST for treating total limbal stem cell deficiency. Deficiency types included Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (SJS/TEN; n = 80), ocular surface burns (Burn; n = 75), ocular cicatricial pemphigoid (OCP) or pseudo-OCP (n = 58), and others (n = 33). The methods of CCST included 103 cultivated limbal epithelial transplantations (28 autologous, 62 allogeneic, and 13 living-related relatives), and 143 cultivated oral mucosal epithelial transplantations. We analyzed the rate of successful ocular surface reconstruction, clear corneas, and best-corrected visual acuity equal to or better than 20/200. RESULTS: With a mean observation period of 357 weeks, successful ocular surface reconstruction and clear corneas at last visit were achieved in 65.1% of the patients. Corrected visual acuity equal to or better than 20/200 was achieved in 19.0% of the patients. Eyes with SJS/TEN exhibited worse outcomes compared with the Burn group. Postoperative complications included corneal ulcerations or perforations (18.3%), glaucoma (13.8%), and infections (8.5%). Multivariate analyses using the logistic mixed-effects model indicated that the presence of preoperative corneal epithelial defects was a significant risk factor for postoperative failure. CONCLUSIONS: In this series, the success rate of CCST after a mean observation period of 357 weeks was 65.1%, and preoperative epithelial defect was the most relevant risk factor.

Management of acute corneal hydrops after laser in situ keratomileusis.

A 43-year-old man developed acute corneal hydrops after laser in situ keratomileusis (LASIK). A persistently fluid-filled interface between the corneal flap and stroma (without flap dehiscence or wound leakage) did not respond to the conservative treatment. To avoid keratoplasty, the subflap fluid was drained by an air injection into the anterior chamber; the surgery also included suturing of the corneal flap and stroma. The corrected distance visual acuity improved rapidly after resolution of the fluid-filled interface and corneal stromal edema, and no leakage was observed. Thus, a minimally invasive surgery to drain the subflap fluid by an air injection was effective for treating a persistently fluid-filled interface in a case of acute corneal hydrops after LASIK.

A New Perspective on Dry Eye Classification: Proposal by the Asia Dry Eye Society.

The 2017 consensus report of the Asia Dry Eye Society (ADES) on the definition and diagnosis of dry eyes described dry eye disease as "Dry eye is a multifactorial disease characterized by unstable tear film causing a variety of symptoms and/or visual impairment, potentially accompanied by ocular surface damage." The report emphasized the instability of tear film and the importance of visual dysfunction in association with dry eyes, highlighting the importance of the evaluation of tear film stability. This report also discussed the concept of tear film-oriented therapy, which stemmed from the definition, and which is centered on provision of insufficient components in each tear film layer and ocular surface epithelium. The current ADES report proposes a simple classification of dry eyes based on the concept of tear film-oriented diagnosis and suggests that there are three types of dry eye: aqueous-deficient, decreased wettability, and increased evaporation. It is suggested that these three types respectively coincide with the problems of each layer: aqueous, membrane-associated mucins, and lipid/secretory mucin. Although each component cannot be quantitatively evaluated with the current technology, a practical diagnosis based on the patterns of fluorescein breakup is recommended. The Asia Dry Eye Society classification report suggests that for a practical use of the definition, diagnostic criteria and classification system should be integrated and be simple to use. The classification system proposed by ADES is a straightforward tool and simple to use, only through use of fluorescein, which is available even to non-dry eye specialists, and which is believed to contribute to an effective diagnosis and treatment of dry eyes.

Long-Term Safety and Effectiveness of Diquafosol for the Treatment of Dry Eye in a Real-World Setting: A Prospective Observational Study.

INTRODUCTION: Diquafosol is a P2Y2 receptor agonist that has been shown to be effective in the treatment of dry eye disease (DED) in short-term studies; however, its long-term safety and effectiveness have not been evaluated in a real-world setting. METHODS: This prospective, multicentre, open-label observational study was conducted in patients with DED over 12 months. Safety endpoints included the incidence of adverse drug reactions (ADRs) and serious ADRs. Effectiveness endpoints included change from baseline in keratoconjunctival staining score, tear film break-up time (BUT) and Dry Eye-related Quality of Life Score (DEQS). RESULTS: A total of 580 patients were included, most of whom were female (82.9%). The proportion of patients who completed 12 months of observation was 55.0%, the most common reason for discontinuation was patient decision (54.6%). The incidence of ADRs was 10.7% and was highest during the first month of treatment (5.5%); no serious ADRs were reported. Compared with baseline, significant improvements in all effectiveness outcomes, including keratoconjunctival fluorescein staining score, BUT and DEQS summary score, were observed at each evaluation during the treatment period (p < 0.001). CONCLUSION: The present, real-world study showed that diquafosol 3.0% ophthalmic solution was well tolerated and effective in the long-term treatment of DED.

A prospective, randomized clinical study comparing accelerated corneal collagen crosslinking with 5% NaCl hypertonic saline for bullous keratopathy in Asian eyes.

BACKGROUND: We compared the clinical outcomes of accelerated corneal collagen crosslinking (CXL) and 5% NaCl hypertonic saline (HS) for the treatment of symptomatic bullous keratopathy (BK). METHODS: A randomized controlled trial was held at Department of Ophthalmology, Tokyo Dental College Ichikawa General Hospital, Chiba, Japan. Twenty-three eyes of 23 consecutive patients with symptomatic BK were enrolled. The etiology of BK included pseudophakic BK, previous keratoplasty, previous endotheliitis, previous glaucoma surgery, trauma, herpes infection, as well as unknown causes. Eleven eyes received epi-off accelerated CXL (with epithelial abrasion and 18 mW/cm ultraviolet A irradiation for 5 minutes) and 12 eyes received HS instillation. In addition to the usual ophthalmic examination, the best-corrected visual acuity (BCVA) and central corneal thickness (CCT) were determined. The CCT was measured using anterior segment optical coherence tomography before and up to 6 months after treatments. Subjective symptoms of pain, blurred vision, photophobia, and irritation were also recorded. RESULTS: The follow-up was completed for all patients in the CXL group. However, 6 patients in the HS group requested CXL treatments after 3 months. The BCVA was not significantly changed during the study periods in both groups. The CCT was significantly thinner in the CXL group compared to the HS group at 1 and 6 months (P = .015 and 0.144, respectively). Among the subjective symptoms recorded, irritation was significantly lower in the CXL group at 1 month (P = .013). CONCLUSIONS: Accelerated CXL may produce transient improvement in pain and corneal edema in patients with BK.

The Efficacy of 2% Topical Rebamipide on Conjunctival Squamous Metaplasia and Goblet Cell Density in Dry Eye Disease.

Purpose: To clarify the pharmacological effects of 2% rebamipide eye drops on mucosal membrane functions of the ocular surface epithelium, we investigated keratoconjunctival alterations at the cellular level in this study. Methods: Fifteen patients with definite dry eye disease were recruited from outpatient clinics of the Department of Ophthalmology, Ichikawa General Hospital. The patients received treatment with 2% rebamipide eye drops q.i.d for 12 weeks. Symptom score assessment, tear film breakup time, fluorescein and lissamine green ocular surface vital staining, grading of lid wiper epitheliopathy, Cochet-Bonnet corneal sensitivity, assessment of squamous metaplasia grades, and goblet cell density calculations from conjunctival impression cytology samples, as well as evaluation of nucleocytoplasmic ratios and corneal epithelial cells from in vivo confocal microscopy images before and 3 months after treatment were performed. Results: The mean symptom scores, tear film breakup time values, ocular surface fluorescein and lissamine green vital staining scores, and lid wiper scores showed a significant improvement after treatment (P < 0.01). The mean squamous metaplasia grade also showed a significant improvement (1.2 ± 0.1 → 0.3 ± 0.1) 3 months after treatment (P = 0.004). There were similar significant improvements in the mean corneal epithelial cell density (660.1 ± 62.6 → 1015.5 ± 43.5 cells/mm2) (P = 0.002) and nucleocytoplasmic ratios (0.1 ± 0.0 → 0.2 ± 0.0) (P = 0.0042) after treatment. Conclusions: Topical use of 2% rebamipide for 3 months was associated with improvements in ocular surface differentiation due to changes of mucosal functions at the cellular level. These alterations may explain objective and subjective improvements in dry eye disease.