Identification and Analysis of Primary Cilia in the Corneal Endothelial Cells of Patients with Bullous Keratopathy.

PURPOSE: To identify primary cilia in human corneal endothelial cells (CECs) obtained from patients with bullous keratopathy (BK). METHODS: This study involved CEC specimens obtained from 10 eyes of 10 consecutive patients (three males and seven females; mean age: 74.5 years, range: 68-90 years) with BK who underwent Descemet's stripping automated endothelial keratoplasty at Baptist Eye Institute, Kyoto, Japan between August 2019 and September 2020. Three corneal buttons obtained from 3 patients who underwent penetrating keratoplasty for keratoconus were used as 'non-BK' controls. All specimens were evaluated with immunofluorescence staining using an antibody against acetylated α-tubulin. RESULTS: Ciliary expression was observed in six of the 10 CEC specimens; i.e. in two specimens obtained from BK patients after glaucoma surgery (trabeculectomy), in two specimens obtained from patients with Fuchs endothelial corneal dystrophy, and in two specimens obtained from a patient with BK after laser iridotomy for primary angle closure. There was acetylated α-tubulin staining but no hair-like structures in two specimens, and ciliary expression was unknown in two specimens due to the absence of cells. The length of the primary cilia varied between all specimens. In contrast, no primary cilia were observed in the corneal buttons obtained from the three keratoconus patients. CONCLUSION: The findings in this study clearly demonstrate the expression of primary cilia in the CECs of patients afflicted with BK.

Strategic combination of cultivated oral mucosal epithelial transplantation and postoperative limbal-rigid contact lens-wear for end-stage ocular surface disease: a retrospective cohort study.

PURPOSE: To provide the long-term outcome of patients with end-stage severe ocular surface disease (OSD) consecutively treated with cultivated oral mucosal epithelial transplantation (COMET) followed by limbal-rigid contact lens (CL)-wear therapy. DESIGN: Retrospective cohort. METHODS: In 23 eyes of 18 patients with severe OSD who underwent COMET surgery between 2002 and 2019 and who were followed with limbal-rigid CL-wear therapy for at least 1 year postoperative, patient demographics, best-corrected visual acuity (BCVA, logMAR), Ocular Surface Grading Scores (OSGS), surgical indication and adverse events were reviewed. Primary and secondary outcomes were BCVA and OSGS changes at baseline and final examination, respectively. RESULTS: This study involved 16 patients with Stevens-Johnson syndrome and 2 patients with mucous membrane pemphigoid (mean age: 59±15 years). The indications for COMET were as follows: corneal reconstruction for vision improvement (10 eyes (43.5%)), corneal reconstruction for persistent epithelial defect (4 eyes (17.4%)) and conjunctival (fornix) reconstruction for symblepharon release (9 eyes (39.1%)). The mean duration of CL-wear postsurgery was 6.4±3.9 years (range: 1.4 to 13.3 years). The mean BCVA at baseline and at final follow-up was logMAR 1.9±0.5 and 1.3±0.7, respectively (p<0.05). Compared with those at baseline, the OSGSs for symblepharon and upper and lower fornix shortening showed significant improvement at each follow-up time point post treatment initiation. No serious intraoperative or postoperative adverse events were observed. CONCLUSION: In patients afflicted with severe OSD, COMET combined with limbal-rigid CL-wear therapy postsurgery was found effective for vision improvement and ocular surface stabilisation.

Topical Betamethasone Treatment of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis with Ocular Involvement in the Acute Phase.

PURPOSE: To clarify the importance of administering topical steroids for the treatment of Stevens-Johnson syndrome (SJS) / toxic epidermal necrolysis (TEN) with ocular involvement in the acute phase. DESIGN: Retrospective case series. METHODS: Using the medical records of acute SJS/TEN patients treated at the Kyoto Prefectural University of Medicine Hospital, Kyoto, Japan, between July 2006 and July 2017, the ocular findings, topical steroid dosage, systemic steroid dosage, and ocular sequelae were retrospectively examined. The level of cytokines in tear fluid and serum samples was also analyzed. RESULTS: This study involved 13 cases. In 10 cases in whom the clinical courses were recorded before the start of steroid therapy, the mean acute ocular severity score (AOSS: 3 = very severe; 2 = severe; 1 = mild; 0 = none) was 2.8 ± 0.4 points in the severest phase. The mean systemic steroid dose after steroid pulse therapy was 694 ± 386 mg and the mean topical steroid (0.1% betamethasone eye drop and ointment) dose was 13.4 ± 3.3 times daily in the severest phase. Analysis of cytokine levels of 4 cases showed that a cytokine storm occurred in the tear fluid after the steroid pulse therapy. At final follow-up, 16 eyes of 8 patients had a logMAR visual acuity of ≤0, and no serious ocular sequelae were observed. CONCLUSIONS: In patients with SJS/TEN, ocular surface inflammation remains strong even after systemic inflammation has improved post steroid pulse therapy, thus suggesting that both systemic and topical steroid therapy should be administered appropriately.

Limbal-Rigid Contact Lens Wear for the Treatment of Ocular Surface Disorders: A Review.

ABSTRACT: Recently, the prescription of large-diameter rigid gas-permeable contact lenses (CLs), also known as "scleral lenses," "corneoscleral lenses," and "limbal-rigid CLs," is on the rise for the treatment of both moderate and severe ocular surface disorders (OSDs). Compared with scleral lenses, the diameter of limbal-rigid CLs is generally smaller, that is, a diameter ranging from 13.0 to 14.0 mm, and they are designed so that the peripheral edge bears on the limbus. The Suncon Kyoto-CS (Sun Contact Lens Co., Ltd.) is a novel limbal-rigid CL design with multistep curves on the peripheral edge for easy tear exchange during blinking that removes debris and prevents lens clouding or fogging, thus allowing patients to enjoy a longer daily duration of CL wear. In severe OSD cases, limbal-rigid CL wear after surgery is a noninvasive therapeutic approach that can neutralize corneal irregularities, decrease dry eye symptoms, prevent the progression or recurrence of symblepharon, and improve the patient's visual acuity and overall quality of life. Thus, surgeries such as amniotic membrane transplantation and cultivated oral mucosal epithelial transplantation, as well as limbal-rigid CL wear, which is noninvasive, are valuable and effective treatment strategies that can now be applied for the management of patients afflicted with severe OSDs.

Intracrine activity involving NAD-dependent circadian steroidogenic activity governs age-associated meibomian gland dysfunction.

Canonically, hormones are produced in the endocrine organs and delivered to target tissues. However, for steroids, the concept of tissue intracrinology, whereby hormones are produced in the tissues where they exert their effect without release into circulation, has been proposed, but its role in physiology/disease remains unclear. The meibomian glands in the eyelids produce oil to prevent tear evaporation, which reduces with aging. Here, we demonstrate that (re)activation of local intracrine activity through nicotinamide adenine dinucleotide (NAD+)-dependent circadian 3ß-hydroxyl-steroid dehydrogenase (3ß-HSD) activity ameliorates age-associated meibomian gland dysfunction and accompanying evaporative dry eye disease. Genetic ablation of 3ß-HSD nullified local steroidogenesis and led to atrophy of the meibomian gland. Conversely, reactivation of 3ß-HSD activity by boosting its coenzyme NAD+ availability improved glandular cell proliferation and alleviated the dry eye disease phenotype. Both women and men express 3ß-HSD in the meibomian gland. Enhancing local steroidogenesis may help combat age-associated meibomian gland dysfunction.

Long-term outcome of cultivated oral mucosal epithelial transplantation for fornix reconstruction in chronic cicatrising diseases.

BACKGROUND/AIMS: To investigate the long-term outcomes of cultivated oral mucosal epithelial transplantation (COMET) for fornix reconstruction in eyes with chronic cicatrising disease. METHODS: This retrospective cohort study involved 16 eyes of 15 patients who underwent COMET for symblepharon release and fornix reconstruction between June 2002 and December 2008. The mean postoperative follow-up period was 102.1±46.0 months (range: 32-183 months). The treated cicatrising disorders included ocular cicatricial pemphigoid (OCP, five eyes), thermal/chemical injury (three eyes) and other chronic diseases (seven eyes; including recurrent pterygium (two eyes), Stevens-Johnson syndrome (one eye) and graft-versus-host disease (one eye)). Ocular-surface appearance was evaluated before surgery, at 1, 4, 12 and 24 weeks postoperative, and then annually based on the previously reported scoring system. Main outcome measures included overall and disease-specific fornix-reconstruction success probabilities analysed by the Kaplan-Meier survival curve. Symblepharon/fornix-shortening recurrence at 24 weeks postoperative, and its relationship to long-term surgical success was also examined. RESULTS: At 5 years postoperative, the mean±SD overall fornix-reconstruction success probability was 79.6%±10.7%, and success probability for thermal/chemical injury and OCP was 100% and 53.3%±24.8%, respectively (p=0.53, log-rank test). The 3-year success probability was significantly higher in the no-disease-recurrence group at 24 weeks postoperative (13 eyes) than in the disease-recurrence group (three eyes) (100% and 33.3%±27.2%, respectively) (p=0.0073, log-rank test). CONCLUSION: COMET was found to be safe and effective for symblepharon release and long-term fornix reconstruction in eyes with chronic cicatrisation. Although the 5-year success probability differed depend on the underlying disease, ocular-surface appearance at 24 weeks postoperative is a factor for predicting long-term outcome.

A Case of Black Fungal Keratitis Caused by Biatriospora mackinnonii.

PURPOSE: To report a novel case of fungal keratitis caused by Biatriospora mackinnonii (Pyrenochaeta mackinnonii), a dematiaceous fungus (black fungus) that rarely causes dermatological infection, in a patient treated for ocular cicatricial pemphigoid. METHODS: An 81-year-old patient with ocular cicatricial pemphigoid was referred to our hospital because of persistent corneal epithelial defects in his left eye. On examination, a slightly elevated dark lesion in the middle of the erosion and hypopyon was observed in that eye, with smear examination of the obtained specimen revealed a filamentous fungal-like material. Initially, treatment included miconazole and fluconazole ophthalmic solution eye drops, natamycin ophthalmic ointment, and systemic voriconazole, followed surgical scraping of the mass, an anterior chamber lavage, and a subconjunctival injection of miconazole. However, the focus had resistance to the treatment and finally led to corneal perforation; hence, therapeutic penetrating keratoplasty (PKP) was subsequently performed. RESULTS: Mycological testing revealed that the lesions were Candida parapsiliosis and black fungus, with the black fungus classified as B. mackinnonii via DNA sequencing of the internal transcribed spacer and the D1/D2 domains of the 28S rRNA gene. Fungal keratitis caused by B. mackinnonii was resistant to the antifungal drugs, yet was ameliorated by PKP, with no recurrence of fungal keratitis for more than 2 years postoperative. CONCLUSIONS: To the best of our knowledge, this is the first reported case of fungal keratitis caused by B. mackinnonii; however, in this case, PKP surgery resulted in a favorable outcome.

Pterygium excision with modified bare sclera technique combined with mitomycin C.

PURPOSE: Numerous surgical methods, with varying rates of recurrence, have been applied for the treatment of pterygium. Adjuvant mitomycin C (MMC) application has shown promising results in the prevention of recurrence. Here we propose and describe modified bare sclera technique combined with the intraoperative application of MMC for pterygium excision. STUDY DESIGN: Retrospective study. METHODS: Primary pterygium patients who underwent pterygium excision via the bare sclera combined with 0.04% MMC technique from January 2014 to December 2016 were reviewed. In all patients, the subconjunctival pterygium strand was exposed and then sufficiently excised in combination with the safe use of MMC; i.e., the prevention of MMC dilution and diffusion to surrounding tissue. Surgical complications, recurrence rates, and recurrence onset were recorded. RESULTS: This study involved 32 primary pterygium eyes (grade T1 = 22 eyes; 68.7%). The mean postoperative follow-up period was 26.4 ± 14.5 months (range: 12-60 months). MMC was applied for 1-3 min. The mean complete epithelialization was 12.6 ± 7.6 days and no surgical complications were observed. In 1 patient with double-head primary pterygium, recurrence occurred at 15-months postoperative. CONCLUSIONS: The modified bare sclera technique combined with MMC application was found to be safe, effective, and presents good cosmetic appearance for the treatment of primary pterygium when safety points are strictly applied.

Oral Mucosal Epithelial Transplantation and Limbal-Rigid Contact Lens: A Therapeutic Modality for the Treatment of Severe Ocular Surface Disorders.

Stevens-Johnson syndrome, ocular cicatricial pemphigoid, and severe thermal or chemical injury are considered severe ocular surface disorders (OSDs) because they affect the entire ocular surface, including corneal and conjunctival epithelial stem cells. In patients with severe OSDs, the long-term prognosis for limbal transplantation is poor, and the related corneal opacity and cicatrization lead to devastating visual impairment. To date, there is no standardized treatment to improve vision in cases with severe OSD. Investigating novel treatment methods for severe OSDs, our group began cultivated oral mucosal epithelial transplantation in 2002 and developed a limbal-supported rigid-type contact lens that can be applied as a nonsurgical treatment. When used in combination, these treatment methods make it possible to successfully restore vision in cases with severe OSDs.

Microorganism detection and contamination rate of donor eyes in Japan.

PURPOSE: To evaluate the microorganism detection and contamination rate of donor eyes. STUDY DESIGN: Retrospective study. METHODS: In this retrospective study, we reviewed all donor cornea data collected from Kyoto Prefectural University of Medicine (KPUM) Eye Bank, Kyoto, Japan from April 2015 to June 2018, including microbiologic data obtained from conjunctival swabs and preservation medium and findings of postoperative infection from the medical records. RESULTS: During the study period, 77 eyes from 44 deceased individuals (mean age at time of death: 75 ± 17.3 years [range, 30-102 years]) were donated to the KPUM Eye Bank after being harvested using standard safety precautions and disinfection procedures. In 49 of the 77 eyes (63.6%), the conjunctival-swab culture revealed microorganisms, with the 3 most commonly detected being methicillin-resistant Staphylococcus epidermidis (MRSE), methicillin-sensitive S aureus (MSSA), and methicillin-resistant S aureus (MRSA). The data revealed positive microorganism detection in only 4 (5.2%) of the 77 donor-cornea storage-medium cultures. Positive microorganism detection was found in all the age groups, with no statistical difference between the groups (P > .05). In the eyes enucleated ≥ 2.5 h postmortem, a higher positive microorganism detection occurred (P = .03). During the postoperative follow-up period, there was no record of corneal infection. CONCLUSIONS: The preenucleation conjunctival-swab-culture findings revealed that the rate of positive microorganism detection was similar for advanced-age and younger-age donors and that a shorter elapsed time from donor death to postmortem enucleation resulted in less donor-microorganism contamination.

Risk Factors for Corneal Endothelial Cell Loss in Patients with Pseudoexfoliation Syndrome.

This study investigated corneal endothelial cell density (ECD) in pseudoexfoliation (PEX) syndrome patients and evaluated the clinical factors associated with ECD for 51 eyes of 41 phakic patients with pseudoexfoliation (PEX group) and 201 eyes of 117 patients with age-related cataracts (control group) as an age-matched control to the PEX group. Variable clinical factors, including ECD, central corneal thickness (CCT), anterior chamber depth (ACD), number of anti-glaucoma eye drops and severity of PEX, were examined using multivariate analyses. Severity of PEX was as follows: Mild in 28 eyes, Moderate in 16 eyes, and Severe in 7 eyes. The mean ECD was 2,548 ± 409 cells/mm2 in the PEX group and 2,757 ± 282 cells/mm2 in the control group, respectively, and ECD in the PEX group was significantly lower than that in the control group (P = 0.02). Multivariate analyses revealed that the severity of PEX [-176.8, 95% confidence interval (CI) (-244.5, -109.2), P < 0.01] was significantly associated with lower ECD. Accumulation of PEX materials contributed to early corneal endothelial decompensation.

Publisher Correction: Risk Factors for Corneal Endothelial Cell Loss in Patients with Pseudoexfoliation Syndrome.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Five-year follow-up outcomes after Descemet's stripping automated endothelial keratoplasty: a retrospective study.

OBJECTIVE: To assess graft survival and endothelial cell density (ECD) over a 5-year follow-up period after Descemet's stripping automated endothelial keratoplasty (DSAEK). METHODS AND ANALYSIS: This retrospective study involved 130 eyes of 130 consecutive patients with Fuchs endothelial corneal dystrophy (FECD), non-FECD bullous keratopathy (BK) (non-FECD) or BK post-trabeculectomy or tube-shunt surgery (glaucoma with bleb) who underwent DSAEK between August 2007 and January 2012 and were followed for more than 5 years postoperatively. Patients with previous keratoplasty, graft suture failure, primary graft failure, postoperative endophthalmitis and ocular infection were excluded. Graft survival and ECD was then examined in all patients who underwent DSAEK and completed the postoperative follow-up period. The association between clinical factors and 5-year graft survival after DSAEK was analysed with multivariate logistic regression analysis. RESULTS: The overall graft survival rate at 5 years postoperatively was 85%, yet significantly poorer in the glaucoma with bleb eyes (47%) than in the FECD (100%) or non-FECD (90%) eyes (p<0.01, log-rank test). In the FECD, non-FECD and glaucoma with bleb eyes, the mean ECD at 5 years postoperatively was 1054 cells/mm2, 1137 cells/mm2 and 756 cells/mm2, respectively. Multivariate logistic regression analysis showed history of trabeculectomy or tube-shunt surgery and postoperative allograft rejection to be negative factors for graft survival at 5 years after DSAEK (OR 0.01, 95% CI 0.00 to 0.10 and OR 0.02, 95% CI 0.00 to 0.33, respectively). CONCLUSION: Our findings show that at 5 years postoperatively, the surgical outcome after DSAEK was poorer in eyes after trabeculectomy or tube-shunt surgery. TRIAL REGISTRATION NUMBER: UMIN000024891.

Long-term Progression of Ocular Surface Disease in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

PURPOSE: To investigate the details of the long-term progression of ocular surface cicatrization in eyes with ocular sequelae caused by Stevens-Johnson syndrome (SJS)/toxic epidermal necrosis (TEN). METHODS: In 105 eyes of 66 patients with SJS/TEN, the severity of ocular sequelae was retrospectively evaluated using an ocular surface grading score (OSGS) at 2 time points separated by a greater than 5-year interval. The OSGS included 7 ocular surface components (conjunctivalization, neovascularization, opacification, keratinization, symblepharon, and upper/lower conjunctival-sac shortening) evaluated into grades 0 to 3 (maximum total OSGS: 21), with the worsening of each component and total OSGS evaluated at the greater than 5-year interval. Moreover, we evaluated whether upper-tarsus and lid-margin scarring are factors that affect ocular surface cicatrization progression. RESULTS: In 35 (33.3%) of 105 eyes, the total OSGS worsened during the follow-up period. Partial conjunctivalization (score 1-2) progressed more frequently to total conjunctivalization (score 3) than to no conjunctivalization (score 0) (OR [95% CI]; 5.6 [1.6-20.3]). Partial keratinization (score 1-2) also had a high risk of progression into total keratinization (41.0 [6.3-266.5]). In all cases, keratinization progressed only in the eyes with total conjunctivalization (conjunctivalization score 3). Severity of upper-tarsus scarring or lid-margin scarring affected the worsening of the total OSGS. CONCLUSIONS: In 66 patients with chronic-phase SJS/TEN, ocular surface cicatrization progressed in 33.3% of the 105 eyes during the long-term follow-up period of over 5 years. More than 50% of the partial conjunctivalization eyes progressed toward total conjunctivalization. The partial keratinization eyes had a high possibility of progressing to total keratinization; that is, the so-called "end-stage" status.

Safety of retrocorneal plaque aspiration for managing fungal keratitis.

PURPOSE: To evaluate the safety of retrocorneal plaque aspiration in patients with fungal keratitis. STUDY DESIGN: Retrospective study. METHODS: A retrospective case series of fungal keratitis seen at Kyoto Prefectural University of Medicine between November 2013 and September 2018. Patients with retrocorneal plaque who underwent retrocorneal plaque aspiration for the diagnosis and treatment of fungal keratitis were included. The retrocorneal plaques were either aspirated using a tuberculin syringe with a 27-gauge blunt needle or were directly pulled out using a forceps. The anterior chamber was carefully washed out using bimanual irrigation and aspiration (I/A). Diagnosis accuracy and treatment safety were evaluated. RESULTS: Five eyes of five patients aged 68.4 ± 13.0 years old (range: 45-81 years) were included. Three of the five patients (60%) were positive for fungus obtained from corneal scrapings. Retrocorneal plaque aspiration improved the diagnosis accuracy to five out of five patients (100%), including two cases positive to Fungiflora Y® staining. Three of the five patients (60%) had good response rapidly after retrocorneal plaque aspiration, and two patients received therapeutic keratoplasty. All cases were finally stabilized without severe complications. CONCLUSION: Retrocorneal plaque aspiration may be useful for the precise diagnosis of fungal keratitis.

A novel mutation in gelatinous drop-like corneal dystrophy and functional analysis.

We identified a novel mutation of the tumor-associated calcium signal transducer 2 (TACSTD2) gene in a Japanese patient with gelatinous drop-like corneal dystrophy (GDLD). Genetic analysis revealed a novel homozygous mutation (c.798delG, which may result in frameshift mutation p.Lys267SerfsTer4) in the TACSTD2 gene. This mutated gene was devoid of its original function in helping the claudin (CLDN) 1 and 7 proteins transfer from the cytoplasm to the plasma membrane.

Topical non-steroidal anti-inflammatory drugs for the treatment of cystoid macular edema post Descemet's stripping automated endothelial keratoplasty.

PURPOSE: To investigate the effectiveness of topical non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of cystoid macular edema (CME) post Descemet's stripping automated endothelial keratoplasty (DSAEK). STUDY DESIGN: Retrospective observational study METHODS: In this study of 334 patients who underwent DSAEK at the Baptist Eye Institute, Kyoto, Japan between July 2011 and December 2015, 18 patients with postoperative CME (determined by optical coherence tomography) treated with topical NSAIDs after the onset of CME were included. RESULTS: At CME onset, 17 of the 18 patients were treated with bromfenac eye drops and 1 was treated with nepafenac eye drops. Post initiation of treatment with topical NSAIDs, CME in 17 (94.4%) of the 18 patients improved at 1 month and all cases completely recovered within 3 months. At 12-months post initiation of treatment, 61.1% (n = 11) of patients achieved a visual acuity (VA) of 20/40 or better, and there was no significant difference of VA between the patients with or without an episode of postoperative CME (P = 0.55). CONCLUSION: The administration of topical NSAID eye drops was found to be effective in treating patients with CME post DSAEK.

Moderately Long-Term Safety and Efficacy of Repeat Penetrating Keratoplasty.

PURPOSE: To investigate the moderately long-term safety and efficacy of repeat penetrating keratoplasty (PK) for treatment of a failed PK graft. METHODS: Retrospective consecutive clinical case series. Of 992 consecutive cases that underwent PK at Baptist Eye Institute, Kyoto, Japan, between April 1998 and September 2013, 96 cases that underwent repeat PK with more than 3 years postoperatively follow-up were retrospectively reviewed. Surgical outcomes including donor graft survival rate, best spectacle-corrected visual acuity, endothelial cell density, and complications afeter repeat PK were assessed. RESULTS: At 1, 3, and 5 years after repeat PK, the donor graft survival rate was 91%, 75%, and 64%, respectively, and the mean endothelial cell density in those survived grafts was 1778, 1207, and 989 cells/mm, respectively. Best spectacle-corrected visual acuity over 20/200 and 20/40 was achieved in 71% and 27% of the patients, respectively, at 1 year postoperatively, in 59% and 31% of the patients, respectively, at 3 years postoperatively, and in 53% and 29% of the patients, respectively, at 5 years postoperatively. The most common complication for repeat PK was the need for additional glaucoma surgery [n = 11 patients (11.5%)]. Cox proportional hazard regression analyses revealed that previous glaucoma surgery and a rejection episode were high risk factors for graft failure in repeat PK [hazard ratio (HR) = 6.7; 95% confidence interval (CI), 2.1-21.2 and HR = 5.6; 95% CI, 1.8-18.0, respectively]. CONCLUSIONS: Repeat PK provided relatively safe and effective moderately long-term surgical outcomes.

Injection of Cultured Cells with a ROCK Inhibitor for Bullous Keratopathy.

BACKGROUND: Corneal endothelial cell (CEC) disorders, such as Fuchs's endothelial corneal dystrophy, induce abnormal corneal hydration and result in corneal haziness and vision loss known as bullous keratopathy. We investigated whether injection of cultured human CECs supplemented with a rho-associated protein kinase (ROCK) inhibitor into the anterior chamber could increase CEC density. METHODS: We performed an uncontrolled, single-group study involving 11 persons who had received a diagnosis of bullous keratopathy and had no detectable CECs. Human CECs were cultured from a donor cornea; a total of 1×106 passaged cells were supplemented with a ROCK inhibitor (final volume, 300 µl) and injected into the anterior chamber of the eye that was selected for treatment. After the procedure, patients were placed in a prone position for 3 hours. The primary outcome was restoration of corneal transparency, with a CEC density of more than 500 cells per square millimeter at the central cornea at 24 weeks after cell injection. Secondary outcomes were a corneal thickness of less than 630 µm and an improvement in best corrected visual acuity equivalent to two lines or more on a Landolt C eye chart at 24 weeks after cell injection. RESULTS: At 24 weeks after cell injection, we recorded a CEC density of more than 500 cells per square millimeter (range, 947 to 2833) in 11 of the 11 treated eyes (100%; 95% confidence interval [CI], 72 to 100), of which 10 had a CEC density exceeding 1000 cells per square millimeter. A corneal thickness of less than 630 µm (range, 489 to 640) was attained in 10 of the 11 treated eyes (91%; 95% CI, 59 to 100), and an improvement in best corrected visual acuity of two lines or more was recorded in 9 of the 11 treated eyes (82%; 95% CI, 48 to 98). CONCLUSIONS: Injection of human CECs supplemented with a ROCK inhibitor was followed by an increase in CEC density after 24 weeks in 11 persons with bullous keratopathy. (Funded by the Japan Agency for Medical Research and Development and others; UMIN number, UMIN000012534 .).

Topical ganciclovir treatment post-Descemet's stripping automated endothelial keratoplasty for patients with bullous keratopathy induced by cytomegalovirus.

BACKGROUND/AIMS: To investigate the efficacy of topical ganciclovir (GCV) for preventing disease recurrence and improving the surgical outcome post-Descemet's stripping automated endothelial keratoplasty (DSAEK) in patients with cytomegalovirus (CMV) endotheliitis. METHODS: This prospective, non-comparative case series study involved six eyes of six patients with endothelial decompensation due to CMV endotheliitis who underwent DSAEK, followed by a continuous, four to six times daily, topical administration of 0.5% GCV. Patient demographics, clinical history, and preoperative and postoperative examination (including any recurrence of CMV endotheliitis post-DSAEK), best corrected visual acuity (BCVA), intraocular pressure (IOP), graft survival rate and endothelial cell density (ECD) were examined. RESULTS: No recurrence of CMV endotheliitis was detected post-DSAEK. The mean follow-up period was 40 months (range, 12-60 months). The mean preoperative BCVA was 1.52±0.68 LogMAR (range, 0.52-2.40 LogMAR), yet it had significantly improved to 0.15±0.16 LogMAR (range: -0.08 to 0.30 LogMAR) by 1 year postoperative (P<0.01). In all patients, IOP was well controlled (10-20 mm Hg) postsurgery. The mean preoperative donor ECD was 2692±177 cells/mm2, and the mean postoperative ECD was 1974, 1771 and 1174 cells/mm2 for the ECD loss of 26%, 33% and 54% at 6, 12 and 36 months, respectively. No adverse effects were observed associated with the long-term topical administration of GCV. CONCLUSION: The continuous topical application of 0.5% GCV was found to be effective for preventing the recurrence of CMV endotheliitis, and it provided the optimal mid-term clinical outcomes post-DSAEK in patients with CMV endotheliitis. TRIAL REGISTRATION NUMBER: UMIN000026746.