Impact of belantamab mafodotin-induced ocular toxicity on outcomes of patients with advanced multiple myeloma.

Belantamab mafodotin (BLMF) is a B-cell maturation antigen-directed antibody-drug conjugate, recently approved for advanced multiple myeloma (MM). The impact of BLMF-induced ocular toxicity on patient outcomes is unknown. We studied a cohort of 38 consecutively seen patients treated with BLMF outside of trials. Of those, 75% experienced ocular toxicity, with 69% developing keratopathy. Among patients requiring ocular toxicity-related permanent BLMF discontinuation (14%) or dose reduction (11%), 70% had progression of MM within a median of 3 months (95% confidence interval: 0.2-not reached) following BLMF interruption or dose reduction. Ocular toxicity is a major deterrent to the continuous use of BLMF in routine clinical practice. Measures to successfully prevent and mitigate ocular toxicity should be developed to achieve the full potential of this agent.

Impact of Standardized Prescribing Guidelines on Postoperative Opioid Prescriptions after Ophthalmic Surgery.

PURPOSE: To determine the effect of implementing standardized opioid prescribing guidelines on prescription patterns for acute pain after ophthalmic surgery in opioid-naïve patients. DESIGN: Quality improvement study. PARTICIPANTS: Ophthalmic surgeons in an academic department of ophthalmology. METHODS: Postoperative opioid prescribing patterns were compared before and after the implementation of standardized opioid prescribing guidelines for ophthalmic surgery at an academic institution. Only prescriptions provided to opioid-naïve patients 18 years of age or older were included. Surgeons reached a consensus for standardized prescribing guidelines appropriate for the type of surgery within their subspecialty. Guidelines were disseminated in conjunction with postsurgical pain management education to all ophthalmologists in the department, including trainees. The frequency of opioid prescriptions, the quantity of opioid prescribed (converted to oral morphine equivalent [OME]), and opioid prescription refill rates were compared before and after intervention. MAIN OUTCOME MEASURES: Prescriptions with more than 80 OME, frequency of opioid prescriptions, mean OME, and refill rates. RESULTS: Of 5349 ophthalmic surgeries performed during the 2 assessment periods, 196 (3.7%) were associated with opioid prescriptions for acute postoperative pain. The frequency of opioid prescriptions decreased to 3.0% (81/2736) after intervention compared with 4.4% (115/2613) before intervention (P = 0.005). When opioids were prescribed, the mean OME decreased from 93 (range, 27-500) before intervention to 42 (range, 14-100) after intervention (P = 0.003). The number of prescriptions for more than 80 OME decreased from 56 (2.1%) before intervention to 4 (0.1%) after intervention (P < 0.001). Based on the standardized guidelines, 103 of the 115 (89.6%) preintervention opioid prescriptions would not have adhered to the guidelines, whereas 39 of the 81 (48.1%) postintervention prescriptions did not adhere to the guidelines (P < 0.001). The proportion of refill prescriptions did not differ before and after intervention (P = 0.44). CONCLUSIONS: The process of discussing postsurgical pain management and developing standardized opioid prescribing guidelines reduces overprescribing of opioids after ophthalmic surgery without increasing refill rates. Continued education is required to improve adherence to the prescribing guidelines further.

Predicting the Prognosis of Fuchs Endothelial Corneal Dystrophy by Using Scheimpflug Tomography.

PURPOSE: To determine if Scheimpflug tomography pachymetry map and posterior elevation map patterns, central corneal thickness (CCT), and corneal backscatter can predict the prognosis of Fuchs endothelial corneal dystrophy (FECD). DESIGN: Cross-sectional study with follow-up of outcomes. PARTICIPANTS: Ninety-six eyes (56 subjects) with a range of severity of FECD. METHODS: Corneas were graded by cornea specialists according to the area and confluence of guttae and the presence of clinically definite edema. Masked and randomized Scheimpflug imaging pachymetry map and posterior elevation map patterns were assessed by 1 observer for loss of regular isopachs, displacement of the thinnest point of the cornea, and the presence of posterior surface depression. The prognosis of eyes over a 5-year (median) follow-up period was determined based on FECD progression (new onset of clinically definite edema or ≥5% increase in CCT) or intervention by endothelial keratoplasty. Cumulative probabilities of progression and intervention were estimated from survival analyses, with risk factors determined by using Cox proportional hazards models. MAIN OUTCOME MEASURES: Pachymetry map and posterior elevation map patterns, corneal backscatter, and CCT (ultrasonic pachymetry). RESULTS: In univariate analyses, loss of regular isopachs (hazard ratio [HR], 18.00) displacement of the thinnest point (HR, 11.53), focal posterior surface depression (HR, 10.21), and anterior corneal backscatter (HR, 1.22, per 1-grayscale unit increment), were risk factors for progression or intervention (P < 0.001), whereas CCT (HR, 1.30, per 25-µm increment) was not (P = 0.15). In multivariate analyses, loss of regular isopachs (HR, 11.57; P < 0.001) and displacement of the thinnest point (HR, 5.61; P = 0.02) were independent and clinically important risk factors for progression and intervention. The 5-year cumulative risk of disease progression and intervention was 7%, 48%, and 89% when none, 1 or 2, and all 3 pachymetry map and posterior elevation map parameters were present, respectively (P <0.001). The 4-year cumulative risk of disease progression and intervention after uncomplicated cataract surgery was 0%, 50%, and 75% when none, 1 or 2, and all 3 pachymetry map and posterior elevation map parameters were present, respectively (P < 0.001). CONCLUSIONS: Three Scheimpflug tomography pachymetry map and posterior elevation map patterns can predict FECD prognosis independent of CCT. The risk of FECD progression and intervention, including after uncomplicated cataract surgery, increases according to the number of parameters present.

Determining Subclinical Edema in Fuchs Endothelial Corneal Dystrophy: Revised Classification using Scheimpflug Tomography for Preoperative Assessment.

PURPOSE: To determine if Scheimpflug tomography can identify subclinical corneal edema in Fuchs endothelial corneal dystrophy (FECD), and to recommend a new classification of FECD for clinical practice and research. DESIGN: Cross-sectional study with follow-up of outcomes. PARTICIPANTS: Ninety-three eyes from 57 subjects with a range of severity of FECD and 74 eyes from 40 subjects with normal corneas. METHODS: Corneas were clinically assessed for FECD and corneal edema by using slit-lamp biomicroscopy, and categorized as having clinically definite edema (obvious visible edema), being suspicious for subclinical edema (possible corneal thickening without obvious edema on slit-lamp examination), or not having edema (no clinical suspicion of edema). Tomographic pachymetry and elevation maps derived from Scheimpflug images were evaluated by 3 masked observers for specific features believed to be consistent with corneal edema. FECD clinical disease course and outcomes were reviewed from the time of Scheimpflug image acquisition to the last available follow-up. MAIN OUTCOME MEASURES: Presence of tomographic features: (1) loss of parallel isopachs, (2) displacement of the thinnest point of the cornea, and (3) focal posterior corneal surface depression. Clinical outcomes included the change in central corneal thickness (CCT) and vision after endothelial keratoplasty (EK). RESULTS: The 3 specific tomographic features were all present in all FECD corneas with clinically definite edema (n = 15), in ≥81% of FECD corneas suspicious for subclinical edema (n = 16), in ≤42% of FECD corneas deemed not to have edema (n = 62), and in ≤5% of normal corneas (n = 74). Corneas suspicious for subclinical edema that subsequently underwent EK (n = 9) all had at least 2 of the tomographic features present before EK, and improvement in vision, CCT, and tomographic features after EK confirmed the presence of subclinical edema preoperatively. CONCLUSIONS: Subclinical corneal edema in FECD can be detected by Scheimpflug tomography. We recommend classifying FECD corneas as having clinically definite edema (based on slit-lamp examination), subclinical edema (based on tomographic features without clinically definite edema), or no edema (no tomographic or slit-lamp features of edema). This classification is independent of CCT and should be considered when evaluating FECD eyes for cataract surgery or EK.

Postoperative Endothelial Cell Density Is Associated with Late Endothelial Graft Failure after Descemet Stripping Automated Endothelial Keratoplasty.

PURPOSE: To determine whether preoperative endothelial cell density (ECD) and postoperative ECD after Descemet stripping automated endothelial keratoplasty (DSAEK) are associated with late endothelial graft failure (LEGF) in the Cornea Preservation Time Study (CPTS). DESIGN: Cohort study within a multicenter, randomized clinical trial. PARTICIPANTS: A total of 1007 individuals (1223 study eyes), mean age 70 years, undergoing DSAEK for Fuchs' dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (PACE) (6% of eyes) and followed for up to 5 years. METHODS: Central ECD was determined by a central image analysis reading center. Preoperative ECD was determined for 1209 eyes that did not fail and 14 eyes that experienced LEGF. The ECD at 6 and 12 months after DSAEK, the change in ECD from preoperative to 6 and 12 months, surgeon-reported operative complications, and postoperative graft dislocation were investigated for an association with LEGFs unrelated to other postoperative events. Univariable and multivariable Cox proportional hazards regression models were used to assess associations. MAIN OUTCOME MEASURES: Late endothelial graft failure and its associations with pre- and postoperative ECD and operative complications. RESULTS: The cumulative probability of LEGF was 1.3% (95% confidence interval [CI], 0.8%-2.4%). Median (interquartile range [IQR]) preoperative ECDs were similar for eyes with LEGF (2523; 2367-3161) cells/mm2) and eyes without failure (2727; 2508-2973) cells/mm2) (P = 0.34). The ECD at 6 months was associated with LEGF (P < 0.001) in time-to-event analyses, whereas preoperative ECD was not (P = 0.55). The cumulative incidence (95% CI) of LEGF was 6.5% (3.0%, 14.0%) for 97 grafts with a 6-month ECD less than 1200 cells/mm2, 0.3% (0.0%, 2.4%) for 310 grafts with a 6-month ECD between 1200 and 2000 cells/mm2, and 0.6% (0.1%, 2.7%) for 589 grafts with a 6-month ECD greater than 2000 cells/mm2. In multivariable analyses, ECD at 6 months and operative complications were both associated with LEGF (P = 0.002 and P = 0.01, respectively), whereas graft dislocation was not (P = 0.61). CONCLUSIONS: In eyes undergoing DSAEK, preoperative ECD is unrelated to LEGF, whereas lower ECD at 6 months is associated with LEGF. Early endothelial cell loss after DSAEK and intraoperative complications should be minimized to improve graft survival.

The impact of paediatric antimicrobial stewardship programmes on patient outcomes.

PURPOSE OF REVIEW: Although there has been an unprecedented global effort to reduce the spread of antimicrobial resistance, little emphasis has been placed on children. This review aims to evaluate the impact of paediatric antimicrobial stewardship programmes as well as providing a practical approach for effectively implementing them in community-based settings and in hospitals. RECENT FINDINGS: Although rates of serious bacterial infection are low in children, the rates of antimicrobial use and resistance are comparable with adults. Different strategies are required to implement antimicrobial stewardship in community-based settings compared to in hospitals. Nationally coordinated, whole-system approaches have achieved long-term, sustainable reductions in antimicrobial prescribing, as well as reductions in resistance rates at population level, with no evidence of an increase in rate of serious infection or bacterial complications. SUMMARY: Antimicrobial stewardship programmes in neonates and children have unique characteristics and issues. There is currently no consensus on how to measure consumption of antimicrobials in neonates and children. This is a research priority. Benchmarking and clinical networks in neonates and paediatrics are important to share practice and drive best use of antimicrobials.

Patient-Reported Visual Disability in Fuchs' Endothelial Corneal Dystrophy Measured by the Visual Function and Corneal Health Status Instrument.

PURPOSE: Measuring patient-reported visual disability in Fuchs' endothelial corneal dystrophy (FECD) may be helpful in determining when to intervene and for understanding the outcomes of intervention. In this study, we aimed to validate a new patient-reported visual disability questionnaire, the Visual Function and Corneal Health Status (V-FUCHS) instrument, in FECD before and after endothelial keratoplasty (EK). DESIGN: Cross-sectional study with instrument readministration at 6 weeks. PARTICIPANTS: Patients with a range of severity of FECD, including after EK, and patients with healthy corneas. METHODS: The V-FUCHS instrument was developed based on patient interviews, expert consultations, and pretesting. Psychometric methods of classic test theory were applied to estimate reliability and validity, including testing V-FUCHS against Catquest-9SF, a cataract-specific visual disability questionnaire. Ordered polytomous Rasch-based partial credit models and item response theory diagnostics were used to define the response patterns. MAIN OUTCOME MEASURES: Reliability (primary) and validity (secondary). RESULTS: The final instrument was completed by 65% of patients with a range of severity of FECD (n = 41), after undergoing EK for FECD (n = 70), and with healthy corneas (n = 28). Participants were phakic or pseudophakic. Exploratory factor analysis among FECD and patients who underwent EK showed 2 independent factors of visual disability: 7 items related to visual acuity and 8 items related to glare or diurnal variation. Retest reliability was substantial (intraclass correlation coefficient, ≥0.8, both factors). Among all patients, the visual acuity factor was correlated with Catquest-9SF scores (r = 0.65; P < 0.001; n = 96). The glare or diurnal variation factor increased with FECD severity (P < 0.001, n = 69) and was higher in FECD than healthy participants (P < 0.001). Diagnostics revealed that both factors were well calibrated and met Rasch model expectations. CONCLUSIONS: The V-FUCHS instrument is valid and reliable for assessing visual disability in FECD. The instrument allows for standardized, comprehensive, and rapid assessment of disease-specific visual disability and may be useful in clinical practice and research as a patient-reported outcome measure.

Medical and Semi-surgical Treatments for Fuchs Endothelial Corneal Dystrophy.

Unraveling the genetic mechanisms of Fuchs endothelial corneal dystrophy has opened new possibilities for future targeted medical therapy of the disease. Until these possibilities mature, regenerative semi-surgical approaches by cell injection or cell sheet transfer could help expand the donor pool, and possibly enable autologous transplantation. Descemet membrane stripping alone and acellular Descemet membrane transfer are more immediate surgical approaches that could be temporary treatments in some patients, though there is a lack of understanding of the factors that predict success for these procedures. Regardless of approach, clinical trials will be necessary, and clinicians should therefore try to standardize their methods of assessing disease severity and the outcomes of intervention.

Do Moderate Surgical Treatment Delays Influence Survival in Colon Cancer?

BACKGROUND: Studies examining treatment delay and survival after surgical treatment of colon cancer have varied in quality and outcome, with little evidence available regarding the safety of longer surgical treatment wait times. OBJECTIVE: Our study examined the effect of surgical treatment wait times on survival for patients with stage I to III colon cancer. DESIGN: A subset cohort analysis was performed using data from a prospectively maintained database. SETTINGS: The study was conducted at a tertiary referral center. PATIENTS: Data on all of the patients undergoing elective surgery for stage I to III colon cancer from 2006 to 2015 were collected from a prospectively maintained clinical and administrative database. MAIN OUTCOME MEASURES: We examined the impact of prolonged wait time to surgery on disease-free and overall survival. Patients were divided into 2 groups based on a treatment wait time of ≤30 or >30 days and were compared using a Cox proportional hazards model. A subgroup analysis was performed using alternative treatment delay cutoffs of 60 and 90 days. RESULTS: There were 908 patients with stage I to III colon cancer treated over the study period, with a median treatment wait time of 38 days (interquartile range, 21-61 days); 368 patients were treated within 30 days, and 540 were treated beyond 30 days from diagnosis. In adjusted multivariate analysis, a treatment delay of >30 days was not associated with decreased disease-free survival (HR = 0.89 (95% CI, 0.61-1.3); p = 0.52) or overall survival (HR = 0.82 (95% CI, 0.63-1.1); p = 0.16). Likewise, subgroup analysis using alternative treatment delay cutoffs of 60 and 90 days did not demonstrate an adverse effect on survival. LIMITATIONS: This study was limited by retrospective analysis. CONCLUSIONS: Despite longer median treatment wait times from diagnosis to surgery, with the majority of patients exceeding 30 days and many experiencing delays of 2 to 3 months, no adverse impact on survival was observed. Patients who require additional consultations or investigations preoperatively may safely have their surgery moderately delayed to minimize their perioperative risk without any evidence that this will compromise treatment outcomes. See Video Abstract at http://links.lww.com/DCR/A397.

RNA toxicity and missplicing in the common eye disease fuchs endothelial corneal dystrophy.

Fuchs endothelial corneal dystrophy (FECD) is an inherited degenerative disease that affects the internal endothelial cell monolayer of the cornea and can result in corneal edema and vision loss in severe cases. FECD affects ∼5% of middle-aged Caucasians in the United States and accounts for >14,000 corneal transplantations annually. Among the several genes and loci associated with FECD, the strongest association is with an intronic (CTG·CAG)n trinucleotide repeat expansion in the TCF4 gene, which is found in the majority of affected patients. Corneal endothelial cells from FECD patients harbor a poly(CUG)n RNA that can be visualized as RNA foci containing this condensed RNA and associated proteins. Similar to myotonic dystrophy type 1, the poly(CUG)n RNA co-localizes with and sequesters the mRNA-splicing factor MBNL1, leading to missplicing of essential MBNL1-regulated mRNAs. Such foci and missplicing are not observed in similar cells from FECD patients who lack the repeat expansion. RNA-Seq splicing data from the corneal endothelia of FECD patients and controls reveal hundreds of differential alternative splicing events. These include events previously characterized in the context of myotonic dystrophy type 1 and epithelial-to-mesenchymal transition, as well as splicing changes in genes related to proposed mechanisms of FECD pathogenesis. We report the first instance of RNA toxicity and missplicing in a common non-neurological/neuromuscular disease associated with a repeat expansion. The FECD patient population with this (CTG·CAG)n trinucleotide repeat expansion exceeds that of the combined number of patients in all other microsatellite expansion disorders.

Descemet Stripping Endothelial Keratoplasty for Fuchs' Endothelial Corneal Dystrophy: Five-Year Results of a Prospective Study.

PURPOSE: To determine 5-year outcomes of Descemet stripping endothelial keratoplasty (DSEK) for Fuchs' endothelial corneal dystrophy (FECD). DESIGN: Prospective cohort study. PARTICIPANTS: Fifty-two eyes of 45 subjects with FECD undergoing primary DSEK. METHODS: Subjects were examined before and at fixed intervals through 60 months after DSEK. At each visit, graft survival was determined by slit-lamp examination; best spectacle-corrected visual acuity (BSCVA) was measured using the electronic Early Treatment Diabetic Retinopathy Study (ETDRS) protocol; total anterior corneal higher-order aberrations (HOAs) were derived from corneal topography; and corneal backscatter, corneal thickness, and endothelial cell density were measured from confocal microscopy images. Corneal thickness also was measured by ultrasonic pachymetry. Changes after DSEK were analyzed using generalized estimating equation models. MAIN OUTCOME MEASURES: Best-corrected visual acuity, HOAs, endothelial cell loss, corneal thickness, and corneal backscatter. RESULTS: Complete 60-month follow-up was possible in 34 eyes. Mean BSCVA±standard deviation improved from 0.45±0.19 logarithm of the minimum angle of resolution (logMAR) (Snellen equivalent, 20/56) before DSEK to 0.09±0.13 logMAR (Snellen equivalent, 20/25) at 5 years (P < 0.001). Between 1 and 5 years, BSCVA improved by 0.06 logMAR (or 3 ETDRS letters; 95% confidence interval, 0.05-0.07 logMAR) per year (P < 0.001), and 56% of eyes were 0.1 logMAR (20/25) or better at 5 years. Graft thickness (approximately 155 µm) and corneal thickness (approximately 700 µm) did not change after surgery. Anterior corneal HOAs and backscatter decreased between 1 and 5 years (P ≤ 0.002). Six grafts failed, of which 4 were primary (iatrogenic); mean endothelial cell loss±standard deviation was 55±15% at 5 years. CONCLUSIONS: Between 1 and 5 years after DSEK, BSCVA continues to improve such that at 5 years, more than half of eyes see better than 20/25 with a mean total corneal thickness of 700 µm. Improvement in vision is accompanied by continued reduction in corneal haze and aberrations, suggesting ongoing remodeling of the cornea after restoration of endothelial function.

High temperature mass detection using a carbon nanotube bilayer modified quartz crystal microbalance as a GC detector.

A small, portable gas chromatograph (GC) was assembled for the trace detection of controlled substances using a novel quartz crystal microbalance sensor (QCM). The QCM crystal surface was modified with a variety of sorption materials to increase adsorption thereby amplifying mass detection. Single polymer thin film coatings increased the QCM response by 1-2 orders of magnitude, while operating at over 100 °C. Adding a layer of carbonaceous nanomaterial (graphene or carbon nanotubes) above such a film dramatically increased sensitivity by up to 3 orders of magnitude compared to uncoated crystals. Separation and detection of submicrogram quantities of controlled substances was carried out within minutes by employing a GC column and detector temperature ramp up to 220 °C. An additional 10-fold enhancement in sensitivity was achieved by mechanical abrasion of the sample swabs used in the sample introduction process. This study demonstrated a novel use of a polymer composite modified QCM as a chemical sensor at high temperatures.

Corneal High-Order Aberrations and Backscatter in Fuchs' Endothelial Corneal Dystrophy.

PURPOSE: Suboptimal visual acuity after endothelial keratoplasty has been attributed to increased anterior corneal high-order aberrations (HOAs). In this study, we determined anterior and posterior corneal HOAs over a range of severity of Fuchs' endothelial corneal dystrophy (FECD). DESIGN: Cross-sectional study. PARTICIPANTS: A total of 108 eyes (62 subjects) with a range of severity of FECD and 71 normal eyes (38 subjects). METHODS: All corneas were examined by using slit-lamp biomicroscopy to determine the severity of FECD versus normality. Fuchs' endothelial corneal dystrophy corneas were categorized as mild, moderate, or advanced according to the area and confluence of guttae and the presence of clinically visible edema. Normal corneas were devoid of any guttae. Wavefront errors from the anterior and posterior corneal surfaces were derived from Scheimpflug images and expressed as Zernike polynomials through the sixth order over a 6-mm diameter optical zone. Backscatter from the anterior 120 µm and posterior 60 µm of the cornea also was measured from Scheimpflug images and was standardized to a fixed scatter source. Variables were compared between FECD and control eyes by using generalized estimating equation models to adjust for age and correlation between fellow eyes. MAIN OUTCOME MEASURES: High-order aberrations, expressed as root mean square of wavefront errors, and backscatter of the anterior and posterior cornea. RESULTS: Total anterior corneal HOAs were increased in moderate (0.61±0.27 µm, mean ± standard deviation; P = 0.01) and advanced (0.66±0.28 µm; P = 0.01) FECD compared with controls (0.47±0.16 µm). Total posterior corneal HOAs were increased in mild (0.22±0.09 µm; P = 0.017), moderate (0.22±0.08 µm; P < 0.001), and advanced (0.23±0.09 µm; P < 0.001) FECD compared with controls (0.16±0.03 µm). Anterior and posterior corneal backscatter were higher for all severities of FECD compared with controls (P ≤ 0.02, anterior; P ≤ 0.001, posterior). CONCLUSIONS: Anterior and posterior corneal HOAs and backscatter are higher than normal even in early stages of FECD. The early onset of HOAs in FECD might contribute to the persistence of HOAs and incomplete visual rehabilitation after endothelial keratoplasty.

Scleral lenses in the management of ocular surface disease.

PURPOSE: To describe the management of ocular surface disease with commercially available scleral lenses. DESIGN: Retrospective case series at a tertiary referral center. PARTICIPANTS: A total of 212 patients (346 eyes) who were evaluated for scleral lens therapy for the management of ocular surface disease between June 1, 2006, and November 30, 2011. METHODS: Retrospective review of medical records and analysis of a survey mailed to all patients who completed the scleral lens fitting process to evaluate the long-term success of scleral lens therapy in the management of ocular surface disease. MAIN OUTCOME MEASURES: Therapeutic outcome of scleral lens therapy, improvement in visual acuity with scleral lenses, indications for scleral lens wear, and efficiency of fitting process. RESULTS: Of the 212 subjects, 115 (188 eyes) successfully completed the scleral lens fitting process, and therapeutic goals (improved comfort, ocular surface protection, or resolution of keratopathy) were achieved in all but 2 of these subjects. Visual acuity improved with scleral lens wear, from 0.32 ± 0.37 logarithm of the minimal angle of resolution (logMAR) (mean ± standard deviation; Snellen equivalent, 20/42) with habitual correction to 0.12 ± 0.19 logMAR (Snellen equivalent, 20/26) with scleral lenses (P<0.001). The most common indications for scleral lens therapy were undifferentiated ocular surface disease, exposure keratopathy, and neurotrophic keratopathy. Subjects had attempted an average of 3.2 (range, 0-8) other forms of intervention before scleral lens wear. Scleral lens fitting was completed in an average of 3 visits (range, 2-6), with an average of 1.4 lenses/eye (range, 1-4). Three patients experienced complications during scleral lens wear that resolved without loss of visual acuity, enabling resumption of scleral lens wear. CONCLUSIONS: Commercially available scleral lenses can be successfully used in the management of moderate to severe ocular surface disease. The scleral lens fitting process can be completed efficiently for most eyes by using diagnostic trial lenses. In addition to protecting the ocular surface, scleral lenses improve visual acuity in patients whose surface disease has compromised vision.

Corneal abnormalities early in the course of Fuchs' endothelial dystrophy.

PURPOSE: Corneas with advanced Fuchs' endothelial dystrophy that require endothelial keratoplasty manifest anterior corneal structural and cellular abnormalities that have been associated with visual deficits before and after endothelial keratoplasty. In this study, we determined the onset of these abnormalities in the course of the disease. DESIGN: Cross-sectional study. PARTICIPANTS: Sixty-three eyes (39 subjects) with a range of severity of Fuchs' dystrophy and 25 eyes (13 subjects) with normal corneas. METHODS: All corneas were examined using slit-lamp biomicroscopy, ultrasonic pachymetry, and confocal microscopy. The clinical grade of Fuchs' dystrophy was assessed according to the presence and extent of guttae and clinically evident edema and was categorized as mild (grades 1 and 2), moderate (grades 3 and 4), or advanced (grades 5 and 6). Normal corneas were devoid of any central guttae (grade 0). Corneal backscatter (haze) was measured from the confocal image light intensity profile. Stromal cell density and number and the presence of abnormal subepithelial cells were determined from confocal images. Comparisons between groups were made by using generalized estimating equation models. MAIN OUTCOME MEASURES: Anterior corneal backscatter, stromal cell density and number, presence of subepithelial cells, and central corneal thickness. RESULTS: Anterior corneal backscatter was 18% to 67% higher in eyes with moderate and advanced Fuchs' dystrophy compared with normal eyes (P ≤ 0.003); a similar trend was noted in mild Fuchs' dystrophy eyes compared with normal eyes (P = 0.08). Stromal cell density and the absolute number of stromal cells in the anterior 10% of the stroma were approximately 20% and 27% lower, respectively, in Fuchs' dystrophy (regardless of severity) compared with normal (P < 0.001). Abnormal subepithelial cells were visible in 9%, 19%, and 30% of corneas with mild, moderate, and advanced Fuchs' dystrophy, respectively. Only corneas with advanced Fuchs' dystrophy were thicker than normal (P < 0.001). CONCLUSIONS: Anterior corneal cellular and structural abnormalities begin early in the course of Fuchs' dystrophy, before the onset of clinically evident edema. The chronicity of these changes can explain their incomplete resolution after endothelial keratoplasty, and understanding the onset of these may help to determine the optimal time to intervene to achieve best outcomes.

Vision-related quality of life before and after keratoplasty for Fuchs' endothelial dystrophy.

PURPOSE: To assess vision-related quality of life in Fuchs' dystrophy and changes in vision-related quality of life after 3 types of keratoplasty (penetrating keratoplasty [PK], deep lamellar endothelial keratoplasty [DLEK], and Descemet stripping endothelial keratoplasty [DSEK]). DESIGN: Prospective, observational case series. PARTICIPANTS: Sixty-three subjects with Fuchs' endothelial dystrophy: 12 subjects (12 eyes) received PK, 11 subjects (11 eyes) received DLEK, and 40 subjects (40 eyes) received DSEK. METHODS: Subjects were examined before keratoplasty and at regular intervals through 3 years after keratoplasty. At each examination, vision-related quality of life was assessed using the 25-item National Eye Institute Visual Functioning Questionnaire; best spectacle-corrected and uncorrected visual acuities were measured by using the electronic Early Treatment of Diabetic Retinopathy Study protocol; keratometric cylinder was measured by a manual keratometer. Disability glare was measured with a straylight meter. MAIN OUTCOME MEASURES: Vision-related quality of life composite score. RESULTS: Vision-related quality of life composite score for all eyes with Fuchs' dystrophy before keratoplasty was 72 ± 11 (n = 63) and did not differ between groups (P = 0.88). Vision-related quality of life improved by 6 months (PK, P = 0.008; DLEK, P = 0.03; DSEK, P < 0.001), with continued improvement between 6 months and 3 years after PK (P = 0.01) and DSEK (P = 0.004). At 6 months, the composite score was higher after DSEK than after PK (P = 0.006). At 3 years, there were no differences in composite scores between the 3 treatments (P = 0.33; mean minimum detectable difference, 8 [α = 0.05; ß = 0.20]). After keratoplasty, quality of life was correlated with uncorrected visual acuity at 1 year (r = -0.38; P = 0.001) and at 3 years (r = -0.36; P = 0.02), with disability glare at 3 years (r = -0.41; P = 0.02), and with best-corrected visual acuity at 6 months (r = -0.34; P = 0.03), but not thereafter. CONCLUSIONS: Vision-related quality of life in patients with Fuchs' endothelial dystrophy is significantly impaired but improves after keratoplasty, irrespective of the technique. The improvement is faster after DSEK than after PK, and this might be explained in part by rapid improvement in uncorrected visual acuity after DSEK. This study affirms an advantage of endothelial keratoplasty over PK with respect to patient-reported outcomes.