Mini-Scleral Lens: An Effective Mode of Visual Rehabilitation in Eyes With Resolved Hydrops.

OBJECTIVES: To evaluate the visual outcome of mini-scleral contact lenses (MSLs) in keratoconus following the resolution of acute hydrops. METHODS: This was a prospective observational case series of patients of healed hydrops in keratoconus fitted with an MSL (Keracare, Acculens, Lakewood, CO) who were managed for acute hydrops medically or surgically at least 3 months prior. Uncorrected visual acuity, best spectacles-corrected visual acuity, best lens-corrected visual acuity, topographic indices, keratometric indices, contact lens parameters, and ocular aberrometric changes were evaluated. All patients were followed up for at least 3 months. RESULTS: Eighteen eyes of 17 patients were included in the analysis. The mean post-hydrops topographic values of the eyes included flat keratometric value (K1) 64.93±10.88 (range 44.30-93.40) diopters (D), steep keratometric value (K2) 70.41±10.92 D (range 45.8-98.6 D), and Kmax of 79.53±17.73 D (range 50-130.2). The final mini-scleral lens's mean dioptric power was -8.56±3.96 D (range -18 to -4). Visual acuity significantly improved from post-hydrops resolution uncorrected visual acuity of 1.5±0.71 logMAR to 0.79±0.18 logMAR best spectacles-corrected visual acuity to 0.27±0.01 logMAR best lens-corrected visual acuity ( P -value <0.0001). Similarly, there was considerable improvement in corneal aberrometric values after wearing an MSL. At the 3-month follow-up, 15 patients (16 eyes) were compliant to contact lens use with a minimum of 6 to 8 hr daily while two patients (2 eyes) were poorly compliant. CONCLUSIONS: A MSL is a valuable option for visual rehabilitation in keratoconus following the resolution of acute hydrops.

Scleral lens induced short term corneal changes in eyes with Pellucid Marginal Degeneration.

PURPOSE: To investigate the short-term effect of scleral lens (SL) on corneal curvature and corneal oedema in Pellucid Marginal Degeneration (PMD) eyes. METHODS: Corneal anterior, posterior curvature and corneal thickness were measured in 14 eyes of 14 PMD participants with Schiempflug imaging at different corneal diameters and meridians at baseline and after 6 h of SL wear. RESULTS: There was a significant flattening (up to 0.26 mm) of the anterior corneal curvature noted in the inferotemporal quadrant (from 210 to 255 degree at 2 mm, 8 mm and 10 mm corneal diameter), inferonasal quadrant (from 285 to 345 degree at 6 mm and 8 mm corneal diameter), and inferiorly at 2 mm and 10 mm corneal diameter (p < 0.05). Similarly, posterior corneal curvature showed statistically significant steepening mostly in inferotemporal quadrants (from 195 to 255 degree from 4 mm to 8 mm corneal diameter) and inferonasally at 2 mm and 4 mm corneal diameter (p < 0.05). A statistically significant increase in the corneal thickness noted in different corneal diameters with corneal oedema ranging from 2.10 % to 4.00 % after 6 h of SL wear. A gradual increase in corneal oedema was noted form centre to periphery. The baseline central fluid reservoir thickness (FRT) was 341.07 ± 139.8 which reduced to 276.71 ± 114.32 µm after 6 h of lens wear. No significant correlation was noted between corneal oedema with different parameters like initial and final FRT, change in anterior and posterior corneal curvature, and lens thickness (p > 0.05). CONCLUSIONS: Short-term SL wear induced a clinically acceptable range of corneal oedema. A clinically significant flattening in anterior curvature and minimal steepening in posterior curvature were noted. Practitioners should be careful while measuring corneal parameters in PMD eyes wearing SL, as these alterations can provide false impression of disease progression.

How Would Nature See Our Corneal Triumphs? The LXXIX Edward Jackson Lecture.

PURPOSE: To describe discrepancies between clinical observation and current teachings in corneal endothelial disease, particularly in Fuchs endothelial dystrophy and its potential association with primary open angle glaucoma. DESIGN: Perspective. METHODS: A perspective is presented on Fuchs dystrophy, a disorder that commonly presents with a compromised endothelium but minimal stromal edema, indicating that the corneal imbibition pressure is relatively "too high." RESULTS: The discrepancy between the relative lack of stromal edema in the absence of an endothelial cell layer cannot be explained by the current theories involving a circulatory pumping mechanism over the endothelial cell layer, but may point to the following: (1) secondary involvement of the corneal endothelium in Fuchs dystrophy; (2) separate hydration systems for maintaining the imbibition pressure (vertical static hydration) and corneal nutrition (horizontal dynamic hydration); (3) the cornea as net contributor of aqueous humor; (4) a close relationship between the corneal imbibition and intraocular pressure, with potentially a shared regulatory system; and (5) a potential steroid-type hormone dependency of this regulatory system. CONCLUSIONS: Clinical observation shows that the stromal imbibition pressure is "too high" in Fuchs endothelial dystrophy, indicating that it may not primarily be an endothelial disease, but a type of "corneal glaucoma."

Alterações oculares decorrentes de picada de abelha na córnea / Ocular changes due to corneal bee sting

RESUMO O propósito deste estudo foi reportar as alterações oculares observadas após picada de abelha com ferrão retido na córnea. Destacamos o tratamento e o desfecho de uma lesão de córnea incomum e sua patogênese. Trata-se de relato de caso e revisão da literatura de lesões oculares por picada de abelha. Paciente do sexo feminino, 63 anos, procurou atendimento oftalmológico de urgência devido à picada de abelha na córnea do olho direito há 6 dias. Queixava-se de embaçamento visual, dor e hiperemia ocular. Apresentou acuidade visual de vultos no olho afetado. Ao exame, notaram-se hiperemia moderada de conjuntiva bulbar, edema corneano com dobras de Descemet e presença do ferrão alojado na região temporal, no estroma profundo da córnea. A paciente foi internada para ser abordada no centro cirúrgico sob anestesia geral. Durante a cirurgia, o ferrão teve que ser retirado via câmara anterior, mediante a realização de uma paracentese e uma lavagem da câmara anterior, com dupla via e solução salina balanceada. Ainda não existe na literatura um tratamento padrão na abordagem de pacientes com lesões oculares por picada de abelha, sendo importantes a identificação e o reconhecimento precoce de possíveis complicações que ameacem a visão.

ABSTRACT The purpose of this study was to report the ocular changes observed after a bee sting with a stinger retained in the cornea. We show the treatment and outcome of an unusual corneal injury and its pathogenesis. This is a case report and literature review of ocular injuries caused by bee stings. A 63-year-old female patient sought emergency ophthalmic care because of a bee sting on the cornea of her right eye six days before. She complained of blurred vision, pain, and ocular hyperemia. She had glare sensitivity on visual acuity in the affected eye. Examination revealed moderate hyperemia of the bulbar conjunctiva, corneal edema with Descemet's folds and a stinger lodged in the temporal region, in the deep stroma of the cornea. The patient was admitted to the operating room under general anesthesia. During surgery, the stinger had to be removed via the anterior chamber, by performing a paracentesis and washing the anterior chamber with a double flushing and balanced saline solution. There is still no standard treatment in the literature for patients with eye injuries caused by bee stings, and early identification and recognition of possible sight-threatening complications is important.

Inducible Slc4a11 Knockout Triggers Corneal Edema Through Perturbation of Corneal Endothelial Pump.

Purpose: The conventional Slc4a11 knockout (KO) shows significant corneal edema at eye opening, a fact that complicates the study of the initial events leading to edema. An inducible KO would provide opportunities to examine early events following loss of Slc4a11 activity. Methods: Slc4a11 Flox (SF) mice were crossed with mice expressing the estrogen receptor Cre Recombinase fusion protein and fed tamoxifen (Tm) for two weeks. Corneal thickness (CT) was measured by OCT. At eight weeks endpoint, oxidative damage, tight junction integrity, stromal lactate concentration, endothelial permeability, differentially expressed transporters, and junction proteins were determined. Separately, a keratocyte only inducible Slc4a11 KO was also examined. Results: At four weeks post-Tm induction Slc4a11 transcript levels were 2% of control. Corneal thickness increased gradually and was 50% greater than Wild Type (WT) after eight weeks with significantly altered endothelial morphology, increased nitrotyrosine staining, significantly higher stromal lactate, decreased expression of lactate transporters and Na-K ATPase activity, higher ATP, altered expression of tight and adherens junctions, and increased fluorescein permeability. No significant differences in CT were found between WT and keratocyte only Slc4a11 KO. Conclusions: The Slc4a11 inducible KO shows development of a similar phenotype as the conventional KO, thereby validating the model and providing a tool for further use in examining the sequence of cellular events by use of noninvasive in vivo physiological probes.

Randomized, Double-Masked, Pilot Study of Netarsudil 0.02% Ophthalmic Solution for Treatment of Corneal Edema in Fuchs Dystrophy.

PURPOSE: To evaluate off-label use of netarsudil 0.02% for treatment of corneal edema associated with Fuchs dystrophy. DESIGN: Prospective, randomized clinical trial. METHODS: Twenty-nine subjects with symptomatic Fuchs dystrophy were enrolled and randomized to use netarsudil or placebo eye drops once daily for 3 months. The primary outcomes were the change in central corneal thickness between baseline and 1 month and between baseline and 3 months. Secondary outcomes included change in scotopic corrected distance visual acuity (CDVA) at 3 months and change in scores on a visual disability questionnaire validated for use with Fuchs dystrophy. RESULTS: Compared with use of placebo, use of netarsudil produced significant reduction in central corneal thickness at 1 month (mean difference, -20 µm; 95% confidence interval, -32 to -9 µm) and 3 months (mean difference, -26 µm; 95% confidence interval, -39 to -12 µm) and significant improvement in scotopic CDVA at 3 months (mean difference +1.6 lines; 95% confidence interval, 0.2-3.0 lines). Scores on the visual disability questionnaire did not change significantly in either arm or differ significantly between arms. One subject assigned to netarsudil had baseline epithelial bullae and withdrew from the study because of disabling glare. CONCLUSIONS: Use of netarsudil was associated with reduction of corneal edema and improvement in scotopic CDVA in Fuchs dystrophy patients. Further study is needed to more fully assess patient satisfaction and visual acuity under various lighting conditions and to compare use of netarsudil with other treatment options such as endothelial keratoplasty.

Transient Reticular Cystic Corneal Epithelial Edema With Topical Netarsudil: A Case Series and Review.

PURPOSE: To describe cases in which netarsudil ophthalmic solution 0.02% precipitated reversible, reticular cystic epithelial edema. METHODS: A retrospective case review at the Brooklyn Veteran's Association Hospital of patients with corneal stromal edema that were treated with netarsudil and subsequently developed cystic epithelial edema. RESULTS: Four male patients with a mean age of 72 ± 8.0 years developed a reticular, honeycomb-like pattern of epithelial edema located in the interpalpebral and inferior cornea. In 3 of 4 patients, epithelial edema arose within 1 month compared with 2 months in 1 patient. New epithelial cysts did not correlate with worsening central corneal thickness and best spectacle-corrected visual acuity in every patient, which was likely due to the location of the cysts. Two of 4 patients developed increased central corneal thickness with worsening best spectacle-corrected visual acuity. In comparison, 1 patient had improvement in both parameters, whereas 1 patient had no significant change. In all cases, there was resolution of the epithelial cysts after discontinuation of netarsudil. CONCLUSIONS: Although rho-kinase inhibitors have been suggested to improve endothelial function, we have documented worsening epithelial cysts in a subset of patients with pre-existing corneal edema. These effects of netarsudil were transient and resolved after discontinuing treatment within 2 weeks in most patients. We hypothesize that the incidence of this adverse finding is more common than previously believed. Nevertheless, large-scale studies are needed to accurately report on the incidence and clinical significance of this novel finding.

Severe Corneal Hydrops With Suspected Posterior Stromal Rupture Managed With Ultrathin Descemet-Stripping Automated Endothelial Keratoplasty.

PURPOSE: To describe severe acute corneal hydrops in a patient with previously undiagnosed keratoconus, in which anterior segment optical coherence tomography (AS-OCT) revealed a protruding ridge of tissue on either side of Descemet membrane (DM) break, treated successfully with ultrathin Descemet-stripping automated endothelial keratoplasty (UT-DSAEK). METHODS: A case report. RESULTS: A 32-year-old man presented with severe corneal hydrops in OS. He was treated conservatively with hypertonic saline. Serial AS-OCT revealed persistent edema and haze overlying a break in DM, with a ridge of protruding tissue on either side. Based on these findings, UT-DSAEK was performed. Intraoperatively, the ridge of tissue remained firmly adhered after DM removal and was felt to possibly represent posterior stroma. The patient's uncorrected visual acuity improved to 20/80. Literature review revealed 1 case with similar AS-OCT findings who underwent penetrating keratoplasty; histopathology was reported to show Descemet scrolls on either side of the break, but our analysis of this and other reports suggest that an additional layer of tissue is contained within the scroll along with DM. CONCLUSIONS: This case demonstrates severe corneal hydrops in the setting of keratoconus, in which AS-OCT revealed a ridge of protruding tissue on either side of a break in DM. UT-DSAEK led to resolution of corneal edema and improvement in stromal haze and visual acuity. Further research is required to determine the precise role of endothelial keratoplasty and potential role of posterior stromal rupture in some cases of acute corneal hydrops.

Five-Year Follow-up of First 11 Patients Undergoing Injection of Cultured Corneal Endothelial Cells for Corneal Endothelial Failure.

PURPOSE: To report the safety and efficacy of a novel cell injection therapy using cultured human corneal endothelial cells (hCECs) for endothelial failure conditions via the report of the long-term 5-year postoperative clinical data from a first-in-humans clinical trial group. DESIGN: Prospective observational study. PARTICIPANTS: This study involved 11 eyes of 11 patients with pseudophakic endothelial failure conditions who underwent hCEC injection therapy between December 2013 and December 2014. METHODS: All patients underwent follow-up examinations at 1 week, 4 weeks, 12 weeks, and 24 weeks and 1 year, 2 years, 3 years, 4 years, and 5 years after surgery. Specific corneal endothelial cell parameters (i.e., corneal endothelial cell density [ECD], coefficient of variation of area, and percentage of hexagonal cells) and central corneal thickness, best-corrected visual acuity (BCVA) on a Landolt C eye chart, and intraocular pressure (IOP) were recorded. MAIN OUTCOME MEASURES: The primary outcome was the change in central ECD after cell injection therapy, and the secondary outcome was corneal thickness, BCVA, and IOP during the 5-year-postoperative follow-up period. RESULTS: At 5 years after surgery, normal corneal endothelial function was restored in 10 of the 11 eyes, the mean ± standard deviation central corneal ECD was 1257 ± 467 cells/mm2 (range, 601-2067 cells/mm2), BCVA improved significantly in 10 treated eyes, the mean visual acuity changed from 0.876 logarithm of the minimum angle of resolution before surgery to 0.046 logarithm of the minimum angle of resolution after surgery, and no major adverse reactions directly related to the hCEC injection therapy were observed. CONCLUSIONS: The findings in this study confirmed the safety and efficacy of cultured hCEC injection therapy for up to 5 years after surgery.

Thickness and Curvature Changes of Human Corneal Grafts in Dextran-Containing Organ Culture Medium Before Keratoplasty.

PURPOSE: To determine the changes of corneal thickness and curvature of human corneal grafts in organ culture medium II, containing dextran T500 6%, before keratoplasty. METHODS: We examined the tomography of 24 corneas from our eye bank transferred from medium I into medium II. Images were repeated hourly during 24 hours using an anterior segment optical coherence tomography. The central corneal thickness (CCT) was measured with the manual measurement tool of the anterior segment optical coherence tomography. The radii of curvature (anterior flat and steep and posterior flat and steep) were measured with a MATLAB self-programmed software for "sterile donor tomography." RESULTS: The mean CCT (±SD) at baseline (T0) was 727 ± 156 µm. It reached 581 ± 103, 506 ± 84, 472 ± 79, and 456±7 µm after 6, 12, 18, and 24 hours, respectively. After 12 hours, 83% of the final deswelling was achieved. The radii of curvature (±SD) at baseline (T0) were (posterior flat, posterior steep, anterior flat, and anterior steep) 6.6 ± 0.5, 6.2 ± 0.5, 7.7 ± 0.4, and 7.4 ± 0.4 mm, respectively. After 24 hours, the radii of curvature reached 6.8 ± 0.1, 6.6 ± 0.3, 7.6 ± 0.1, and 7.4 ± 0.2 mm, respectively. CONCLUSIONS: The kinetics of the deswelling process in medium II follow a hyperbolic curve. Considering a CCT of 506 µm at T12, we assume that a time interval of 12 hours in medium II might be enough for clinical purposes. This result might help to keep storage in medium II as short as possible to escape potential toxic effects of dextran in medium II. The radius of curvature does not seem to change within 24 hours for all measured surfaces.

Descemet Stripping Only Supplemented With Topical Ripasudil for Fuchs Endothelial Dystrophy 12-Month Outcomes of the Sydney Eye Hospital Study.

PURPOSE: To report early safety and efficacy of Descemet stripping only (DSO) supplemented with ripasudil. METHODS: A pre-post clinical trial with a historical control group for time to heal and cell count parameters. The study received ethics approval and was conducted with oversight of a data safety monitoring board. All enrolled patients had a superior endothelial cell count of >1000 cells/mm2 and were symptomatic from the presence of central guttata degrading vision and/or producing glare. DSO was carried out with a peeling technique and not combined with any other intervention. Ripasudil 0.4% was applied topically from day 1 postoperatively at a dose of 6 times/d until corneal clearance. Cases with relapse of edema were permitted to restart on ripasudil at a reduced dose of 2 drops/d for a further 2 weeks. Stopping rules with progression to a corneal graft were established. Baseline ocular and systemic investigations were carried out and repeated at varying intervals to monitor for local and systemic adverse events. RESULTS: Twenty-three eyes of 23 patients met the inclusion criteria and underwent DSO. Twenty-two of 23 eyes achieved corneal clearance at a mean time of 4.1 weeks. In all patients achieving clearance, improvement in vision was recorded. Improvement in mean uncorrected visual acuity was 0.20 Logarithm of the minimum angle of resolution (LogMar), and improvement in mean best spectacle corrected visual acuity was 0.156 LogMar. One patient failed to clear and underwent Descemet membrane endothelial keratoplasty at week 12. Twenty-one of 22 patients achieving corneal clearance expressed satisfaction with the procedure. The commonest systemic side effect of topical ripasudil was gastrointestinal upset (24%), and the commonest local side effect was ocular irritation (43%). No patient experienced a serious adverse event in the course of the trial. Thirty-nine percent of patients experienced a relapse of edema on ceasing ripasudil, with clearance again on recommencing. CONCLUSIONS: This trial of DSO supplemented with ripasudil included local and systemic safety analysis. We judge that this treatment option is emerging as a reliable intervention for select patients with Fuchs' Endothelial Corneal Dystrophy (FECD) with an acceptable safety profile. The observation of relapse edema is strong evidence of a drug effect. The longevity of these results remains unknown.

Objective and Subjective Evaluation of Clinical Performance of Scleral Lens with Varying Limbal Clearance in Keratoconus.

SIGNIFICANCE: This study evaluates how limbal clearance (LC) may impact the clinical performance of scleral lenses based on subjective response on comfort and ocular responses. Limbal zone designs in scleral lenses might affect the integrity of the limbal epithelial tissue as a result of a combined hypoxic and compression-related etiology. PURPOSE: This study aimed to investigate the clinical performance and ocular and subjective responses to the wear of scleral lenses having varying LC. METHODS: Lenses with varying LC with a difference of 50 µm were fitted on and compared among keratoconic participants. The lenses were worn during a 2-week period. Visual analog scales concerning subjective comfort were completed. Ocular surface findings including hyperemia, limbal staining, and corneal swelling were compared. RESULTS: Participants reported greater comfort achieved with high LC. No difference in limbal and bulbar hyperemia was found (P > .05). Corneal response to scleral lens wear with both low and high LCs seems to result in similar perilimbal staining and negative corneal staining. An increase in corneal pachymetric values was noted at the central and peripheral cornea, with no difference between low- and high-LC lenses (all, P < .05). Quadrant-specific analysis indicated that all meridians at both 6 and 8 mm were increased for the low-LC lenses (all, P < .05) and only the temporal region for the high-LC lenses (P = .02). CONCLUSIONS: Limbal clearance may play an important role in subjective performance in scleral lenses but does not impact the degree of hyperemia in either the limbal or bulbar region. Although low LC might result in more compression-related changes to ocular surface, high LC is associated with greater comfort and greater edematous changes. Limbal zone designs in scleral lenses might affect the integrity of the limbal epithelial tissue as a result of a combined hypoxic and compression-related etiology.

Fluid Reservoir Thickness and Corneal Edema during Open-eye Scleral Lens Wear.

SIGNIFICANCE: There is debate concerning corneal oxygenation during scleral lens wear due to the potential additive hypoxic effect of a lens plus a fluid reservoir. This study investigated the agreement between theoretical models and empirical measurements of scleral lens-induced corneal edema with respect to central fluid reservoir thickness. PURPOSE: The purpose of this study was to examine the effect of altering the fluid reservoir thickness on central corneal edema during short-term open-eye scleral lens wear and to compare these empirical measurements with predictive theoretical models. METHODS: Ten participants (age, 30 ± 4 years) with normal corneas wore highly oxygen-permeable scleral lenses (141 Dk ×10 cm O2 (cm)/[(s) (cm) (mmHg)]) on separate days with either a low (mean, 144; 95% confidence interval [CI], 127 to 160 µm), medium (mean, 487; 95% CI, 443 to 532 µm), or high (mean, 726; 95% CI, 687 to 766 µm) initial fluid reservoir thickness. Epithelial, stromal, and total corneal edema were measured using high-resolution optical coherence tomography after 90 minutes of wear, before lens removal. Data were calculated or extracted from published theoretical models of scleral lens-induced corneal edema for comparison. RESULTS: Scleral lens-induced central corneal edema was stromal in nature and increased with increasing fluid reservoir thickness; mean total corneal edema was 0.69% (95% CI, 0.34 to 1.04%), 1.81% (95% CI, 1.22 to 2.40%), and 2.11% (95% CI, 1.58 to 2.65%) for the low, medium, and high thickness groups, respectively. No significant difference in corneal edema was observed between the medium and high fluid reservoir thickness groups (P = .37). "Resistance in series" oxygen modeling overestimated the corneal edema observed for fluid reservoir thickness values greater than 400 µm. CONCLUSIONS: Scleral lens-induced central corneal edema increases with increasing reservoir thickness, but plateaus at a thickness of around 600 µm, in agreement with recent theoretical modeling that incorporates factors related to corneal metabolism.

Postoperative Complications in Medicare Beneficiaries Following Endothelial Keratoplasty Surgery.

PURPOSE: To determine national-level incidence rates of major postoperative complications following endothelial keratoplasty (EK) procedures and to stratify these rates based on EK indications over an 8-year period using Medicare claims data. DESIGN: Retrospective, cohort study. METHODS: Setting: population-based; study population: Medicare beneficiaries aged ≥65 years who underwent EK procedures; main outcome measurements: 1) occurrence of major postoperative complications (i.e., endophthalmitis, choroidal hemorrhage, infectious keratitis, cystoid macular edema [CME], retinal detachment [RD], or RD surgery) following EK surgery; 2) time-to-event analysis for glaucoma surgery; and 3) occurrence of graft complications. RESULTS: A total of 94,829 EK procedures (n = 71,040 unique patients) were included in the analysis. Of the total, 29% of patients had pre-existing glaucoma. The overall 90-day cumulative incidence of postoperative endophthalmitis and choroidal hemorrhage following EK was 0.03% and 0.05%, respectively. The overall 1-year cumulative rates of RD or RD surgery, infectious keratitis, and CME were 1.0%, 0.8%, and 4.1%, respectively. Approximately 7.6%, 12.2%, and 13.8% of all eyes in this study needed glaucoma surgery at 1-, 5-, and 8-years of follow-up, respectively. The probability of glaucoma surgery among patients with pre-existing glaucoma was 29% vs. 8% among those without pre-existing glaucoma at 8 years. The cumulative probabilities of developing any graft complications were 13%, 23.2%, and 27.1% at 1, 5, and 8 years, respectively, of follow-up. On average, patients undergoing EK procedures for a prior failed graft had the highest rate of complications, whereas those with Fuchs' corneal endothelial dystrophy had the lowest. CONCLUSIONS: The incidence of major postoperative complications including endophthalmitis, retinal detachment, and choroidal hemorrhage following EK procedures is low. A high proportion of eyes undergoing EK eventually require glaucoma surgery and experience graft-related complications. Postoperative outcomes are typically worse for patients undergoing EK for prior failed grafts than for those undergoing EK for Fuchs' corneal endothelial dystrophy.

Corneal Endothelial Pump Coupling to Lactic Acid Efflux in the Rabbit and Mouse.

Purpose: Confirm that the corneal endothelial pump uses a lactate-coupled water efflux mechanism. Methods: Corneal thickness, lactate efflux, and stromal [lactate] were measured in de-epithelialized swollen and nonswollen ex vivo-mounted rabbit corneas perfused with bicarbonate-rich and bicarbonate-free Ringers, ouabain, or acetazolamide to determine if the relationships among these parameters were similar to previous data using intact corneas. The role of barrier function was tested by perfusion with calcium-free EGTA. Predictions of [lactate] in endothelial dystrophy were examined in the Slc4a11 knock out mouse. Results: De-epithelialized corneal swelling, lactate efflux, and stromal [lactate] in response to bicarbonate-free Ringers, ouabain, and acetazolamide perfusion had the same relationship as in intact corneas. The absolute amount of lactate efflux and stromal [lactate] in the de-epithelialized corneas was about half of intact corneas. De-epithelialized, swollen corneas deswelled fully with bicarbonate-rich, partially in the presence of acetazolamide, but continued to swell with bicarbonate-free or ouabain. The relationship among corneal thickness, lactate efflux, and [lactate] was the same as with nonswollen de-epithelialized corneas. In intact corneas swollen by perfusion with calcium-free EGTA, the relationship between swelling and lactate flux was the inverse of control corneas. The relationship between corneal swelling and [lactate] of intact corneas exposed to ouabain, but perfused with 7 mM lactate to simulate aqueous humor, was the same as without lactate. Corneal [lactate] in Slc4a11 knock out was twice that of wild type. Conclusions: The corneal endothelial pump works via a lactate efflux mechanism that requires an intact osmotic barrier.

Brittle cornea syndrome: Disease-causing mutations in ZNF469 and two novel variants identified in a patient followed for 26 years.

AIMS: Brittle cornea syndrome (BCS) is a rare autosomal recessive disorder. The aim of this study was to review ZNF469 mutations associated with BCS type 1 to date and to describe an additional case of Czech/Polish background. METHODS: Whole genome sequencing was undertaken to identify the molecular genetic cause of disease in the proband. Sequence variants in ZNF469 previously reported as BCS type 1-causing were searched in the literature, manually curated and aligned to the reference sequence NM_001127464.2. RESULTS: The proband has been reviewed since childhood with progressive myopia and hearing loss. Aged 13 years had been diagnosed with Stickler syndrome. Aged 16.5 years, he developed acute hydrops in the left eye managed by corneal transplantation. At the age of 26, he experienced right corneal rupture after blunt trauma, also managed by grafting. He had a number of secondary complications and despite regular follow-up and timely management, the right eye became totally blind and the left eye had light perception at the last follow-up visit, aged 42. He was found to be a compound heterozygote for two novel mutations c.1705C>T; p.(Gln569*) and c.1402_1411del; p.(Pro468Alafs*31) in ZNF469. In total 22 disease-causing variants in ZNF469 have been identified, mainly in consanguineous families or endogamous populations. Only four probands, including the case described in the current study, harboured compound heterozygous mutations. CONCLUSION: BCS occurs very rarely in outbred populations which may cause diagnostic errors due to poor awareness of the disease. Investigation into the underlying molecular genetic cause in patients with connective tissue disorders may lead to a re-evaluation of their clinical diagnosis.

Brillouin Microscopy Visualizes Centralized Corneal Edema in Fuchs Endothelial Dystrophy.

PURPOSE: To investigate the feasibility of using Brillouin microscopy for assessment of corneal edema in patients with Fuchs endothelial corneal dystrophy (FECD). Brillouin microscopy analyzes the frequency shift of light inelastically scattered by naturally occurring acoustic waves in a small volume of tissue. The resulting frequency shift is a measure of the local hydromechanical properties of the tissue. METHODS: Participants were scanned using a clinical Brillouin imaging system (780 nm laser, 5 mW), and a color-coded map of the mean Brillouin shift laterally across the corneal stroma was created. RESULTS: Brillouin maps of normal subjects (n = 8) were relatively homogeneous, whereas maps of patients with FECD (n = 7) exhibited significantly reduced Brillouin shifts (unpaired t test, P < 0.001) centrally. The mean difference of 83 MHz corresponds to approximately 3.9% higher water content (percentage difference in volume fraction) in central corneas of the FECD group relative to normal subjects. The Brillouin scan of a patient with FECD 1 month after Descemet membrane endothelial keratoplasty measured a 62 MHz increase in Brillouin shift relative to the preoperative level, indicating normalization of corneal hydration. CONCLUSIONS: All patients with FECD scanned exhibited a centralized reduction in Brillouin shift, distinct from the normal subjects measured and consistent with centralized edema characterized by pachymetry. Brillouin scans revealed substantially reduced water content after Descemet membrane endothelial keratoplasty. These results suggest that Brillouin microscopy could aid treatment planning and assessment of FECD. Moreover, corneal hydration mapping may be useful in understanding fluid pump function dynamics of the cornea and developing early interventions for FECD.

Treatment of Acute Corneal Hydrops With Combined Intracameral Gas and Approximation Sutures in Patients With Corneal Ectasia.

PURPOSE: To assess the efficacy and safety of combined intracameral sulfur hexafluoride and full-thickness corneal sutures in the treatment of acute corneal hydrops (CH). METHODS: This is an uncontrolled series of cases with keratoconus (KC), keratoglobus (KG), and pellucid marginal degeneration that presented with CH of recent onset. RESULT: Thirteen patients completed the study. The mean corneal thickness before treatment was 1,310 (Equation is included in full-text article.)556 µm, which significantly reduced to 660 ± 148 µm at week 1 postoperatively (P = 0.001). It took 11.5 ± 6.5 days for corneal edema to resolve with a minimum and maximum of 5 and 24 days, respectively. Corrected distance Snellen visual acuity (CDVA) significantly improved from 0.04 ± 0.03 before treatment to 0.08 ± 0.06 at week 1 (P = 0.035) and continued to improve through month 1 [(0.11 ± 0.05), P = 0.007] and month 3 [(0.15 ± 0.08), P = 0.002]. No patient needed re-treatment with gas injection, and no complication was detected during the follow-up period. CONCLUSIONS: Combined intracameral gas injection and approximation sutures are probably effective and safe for the treatment of acute CH. This treatment results in rapid recovery with very rare complications.

Diurnal Variation in Corneal Edema in Fuchs Endothelial Corneal Dystrophy.

PURPOSE: The extent of diurnal variation in corneal edema in Fuchs dystrophy is unknown. We measured corneal thickness and posterior profile over the course of the day using Scheimpflug imaging. DESIGN: Prospective cohort study. METHODS: Participants with clinically advanced Fuchs dystrophy eyes undergoing endothelial keratoplasty and participants with healthy corneas were assessed around noon the day before surgery and late afternoon, in presumed steady state. After controlled overnight patching to standardize eyelid closure, participants were assessed immediately upon eye opening in hospital the morning of surgery. RESULTS: Directly upon awakening, patients had mean corneal thickness of 663 µm (interquartile range [IQR], 625-707) in Fuchs dystrophy (n = 44) and controls (n = 11) had thickness of 557 µm (IQR, 527-601). In control corneas, there were no systematic changes with time. In Fuchs dystrophy eyes, corneal thickness decreased after awakening. Ninety-five percent of patients can be expected to have a decrease in corneal thickness over the first 4 hours after awakening between 31 µm and 58 µm (95% prediction interval). Posterior Q decreased on average by 0.15 (95% confidence interval [CI], 0.07-0.23) and posterior radius of curvature decreased by 0.20 mm (95% CI, 0.14-0.27) over the first 4 hours, indicating that edema resolution steepened the central posterior cornea. Beyond 4 hours after awakening, corneas no longer changed considerably in Fuchs dystrophy. CONCLUSION: Impaired hydration control in clinically advanced Fuchs dystrophy makes measurements of key corneal parameters unreliable directly after eye opening. Beyond the first hours after eye opening, corneal thickness measurements are unlikely to vary more in Fuchs dystrophy eyes than in normal eyes.