Invasive squamous cell carcinomas and precursor lesions on UV-exposed epithelia demonstrate concordant genomic complexity in driver genes.

Although squamous cell carcinomas (SCC) are the most frequent human solid tumor at many anatomic sites, the driving molecular alterations underlying their progression from precursor lesions are poorly understood, especially in the context of photodamage. Therefore, we used high-depth, targeted next-generation sequencing (NGS) of RNA and DNA from routine tissue samples to characterize the progression of both well- (cutaneous) and poorly (ocular) studied SCCs. We assessed 56 formalin-fixed paraffin-embedded (FFPE) cutaneous lesions (n = 8 actinic keratosis, n = 30 carcinoma in situ [CIS], n = 18 invasive) and 43 FFPE ocular surface lesions (n = 2 conjunctival/corneal intraepithelial neoplasia, n = 20 CIS, n = 21 invasive), from institutions in the US and Brazil. An additional seven cases of advanced cutaneous SCC were profiled by hybrid capture-based NGS of >1500 genes. The cutaneous and ocular squamous neoplasms displayed a predominance of UV-signature mutations. Precursor lesions had highly similar somatic genomic landscapes to SCCs, including chromosomal gains of 3q involving SOX2, and highly recurrent mutations and/or loss of heterozygosity events affecting tumor suppressors TP53 and CDKN2A. Additionally, we identify a novel molecular subclass of CIS with RB1 mutations. Among TP53 wild-type tumors, human papillomavirus transcript was detected in one matched pair of cutaneous CIS and SCC. Amplicon-based whole-transcriptome sequencing of select 20 cutaneous lesions demonstrated significant upregulation of pro-invasion genes in cutaneous SCCs relative to precursors, including MMP1, MMP3, MMP9, LAMC2, LGALS1, and TNFRSF12A. Together, ocular and cutaneous squamous neoplasms demonstrate similar alterations, supporting a common model for neoplasia in UV-exposed epithelia. Treatment modalities useful for cutaneous SCC may also be effective in ocular SCC given the genetic similarity between these tumor types. Importantly, in both systems, precursor lesions possess the full complement of major genetic changes seen in SCC, supporting non-genetic drivers of invasiveness.

Donor, Recipient, and Operative Factors Associated with Graft Success in the Cornea Preservation Time Study.

PURPOSE: To associate donor, recipient, and operative factors with graft success 3 years after Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS). DESIGN: Cohort study within a multicenter, double-masked, randomized clinical trial. PARTICIPANTS: One thousand ninety individuals (1330 study eyes) with a median age of 70 years undergoing DSAEK for Fuchs endothelial corneal dystrophy (94% of eyes) or pseudophakic or aphakic corneal edema (PACE; 6% of eyes). METHODS: Eyes undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0 to 7 days (n = 675) or 8 to 14 days (n = 655). Donor, recipient, and operative parameters were recorded prospectively. Graft failure was defined as regraft for any reason, a graft that failed to clear by 8 weeks after surgery, or an initially clear graft that became and remained cloudy for 90 days. Failure in the first 8 weeks was classified further as primary donor failure or early failure, in the absence or presence of operative complications, respectively. Proportional hazards and logistic regression models were used to estimate risk ratios (RR) and 99% confidence intervals (CIs) for graft failure. MAIN OUTCOME MEASURES: Graft success at 3 years. RESULTS: One thousand two hundred fifty-one of 1330 grafts (94%) remained clear at 3 years and were considered successful. After adjusting for PT, tissue from donors with diabetes (RR, 2.35; 99% CI, 1.03-5.33) and operative complications (RR, 4.21; 99% CI, 1.42-12.47) were associated with increased risk for primary or early failure. Preoperative diagnosis of PACE (RR, 3.59; 99% CI, 1.05-12.24) was associated with increased risk for late failure by 3 years after surgery compared with Fuchs dystrophy. Graft success showed little variation among other factors evaluated, including donor age (RR, 1.19 per decade; 99% CI, 0.91-1.56 per decade), preoperative donor endothelial cell density (RR, 1.10 per 500 cells; 99% CI, 0.74-1.63 per 500 cells), graft diameter (RR, 1.22 per 1 mm; 99% CI, 0.39-3.76 per 1 mm), and injector use for graft insertion (RR, 0.92; 99% CI, 0.40-2.10). CONCLUSIONS: Descemet stripping automated endothelial keratoplasty success in the early and entire postoperative period is more likely when the donor did not have diabetes and was without operative complications and in the long-term postoperative period in recipients with Fuchs dystrophy compared with those with PACE. Mechanisms whereby diabetic donors and PACE recipients reduce the rate of graft success after DSAEK warrant further study.

The effect of donor diabetes history on graft failure and endothelial cell density 10 years after penetrating keratoplasty.

OBJECTIVE: To examine the long-term effect of donor diabetes history on graft failure and endothelial cell density (ECD) after penetrating keratoplasty (PK) in the Cornea Donor Study. DESIGN: Multicenter, prospective, double-masked, controlled clinical trial. PARTICIPANTS: One thousand ninety subjects undergoing PK for a moderate risk condition, principally Fuchs' dystrophy or pseudophakic or aphakic corneal edema, were enrolled by 105 surgeons from 80 clinical sites in the United States. METHODS: Corneas from donors 12 to 75 years of age were assigned by 43 eye banks to participants without respect to recipient factors. Donor and recipient diabetes status was determined from existing medical records. Images of the central endothelium were obtained before surgery (baseline) and at intervals for 10 years after surgery and were analyzed by a central image analysis reading center to determine ECD. MAIN OUTCOME MEASURES: Time to graft failure (regraft or cloudy cornea for 3 consecutive months) and ECD. RESULTS: There was no statistically significant association of donor diabetes history with 10-year graft failure, baseline ECD, 10-year ECD, or ECD values longitudinally over time in unadjusted analyses, nor after adjusting for donor age and other significant covariates. The 10-year graft failure rate was 23% in the 199 patients receiving a cornea from a donor with diabetes versus 26% in the 891 patients receiving a cornea from a donor without diabetes (95% confidence interval for the difference, -10% to 6%; unadjusted P=0.60). Baseline ECD (P=0.71), 10-year ECD (P>0.99), and changes in ECD over 10 years (P=0.86) were similar comparing donor groups with and without diabetes. CONCLUSIONS: The study results do not suggest an association between donor diabetes and PK outcome. However, the assessment of donor diabetes was imprecise and based on historical data only. The increasing frequency of diabetes in the aging population in the United States affects the donor pool. Thus, the impact of donor diabetes on long-term endothelial health after PK or endothelial keratoplasty, or both, warrants further study with more precise measures of diabetes and its complications.

Subjective complaints after cataract surgery: common causes and management strategies.

PURPOSE OF REVIEW: To describe the common causes of, and management strategies for, nonrefractive subjective visual complaints after cataract surgery. RECENT FINDINGS: Over the past decade, clinical observations and ray-tracing models have greatly increased our understanding of positive and negative dysphotopsias after cataract surgery. The primary factor behind positive dysphotopsias is the use of high refractive index square-edge intraocular lenses (IOLs). Primary and secondary factors that underlie negative dysphotopsias are now better characterized, which has led to successful interventions including IOL exchange and Nd:YAG laser anterior capsulotomy. SUMMARY: Positive and negative dysphotopsias occur after implantation of monofocal IOLs, and can rarely be disabling to patients. Visual complaints after multifocal IOL implantation are more common than after monofocal IOL implantation, but still rarely require significant intervention. A better understanding of the risk factors and optical causes of dysphotopsias will allow for IOL design and patient selection that maximize satisfaction after cataract surgery.

Corneal Specialists' Confidence in Identifying Causal Organisms of Microbial Keratitis.

PURPOSE: Microbial keratitis (MK) is a potentially blinding corneal disease caused by an array of microbial etiologies. However, the lack of early organism identification is a barrier to optimal care. We investigated clinician confidence in their diagnosis of organism type on initial presentation and the relationship between confidence and presenting features. METHODS: This research presents secondary data analysis of 72 patients from the Automated Quantitative Ulcer Analysis (AQUA) study. Cornea specialists reported their confidence in organism identification. Presenting sample characteristics were recorded including patient demographics, health history, infection morphology, symptoms, and circumstances of infection. The association between confidence and presenting characteristics was investigated with 2-sample t-tests, Wilcoxon tests, and Chi-square or Fisher's exact tests. RESULTS: Clinicians reported being "confident or very confident" in their diagnosis of the causal organism in MK infections for 39 patients (54%) and "not confident" for 33 patients (46%). Confidence was not significantly associated with patient demographics, morphologic features, or symptoms related to MK. MK cases where clinicians reported they were confident, versus not confident in their diagnosis, showed significantly smaller percentages of previous corneal disease (0% versus 15%, p = 0.017), were not seen by an outside provider first (69% versus 94%, p = 0.015), or had no prior labs drawn (8% versus 33%, p = 0.046), and a significantly larger percentage of cases wore contact lenses (54% versus 28%, p = 0.029). CONCLUSION: In almost half of MK cases, cornea specialists reported lack of confidence in identifying the infection type. Confidence was related to ocular history and circumstances of infection but not by observable signs and symptoms or patient demographics. Tools are needed to assist clinicians with early diagnosis of MK infection type to expedite care and healing.

Factors Associated With Laboratory Test Negativity Following a Transition in Specimen Collection in Microbial Keratitis Cases.

PURPOSE: Negative laboratory results make targeting microbial keratitis treatment difficult. We investigated factors associated with laboratory negativity in patients with microbial keratitis in the context of a transition to a new specimen collection method. METHODS: Microbial keratitis patients with associated laboratory tests were identified in the electronic health record of a tertiary care facility from August 2012 to April 2022. Patient demographics and laboratory results were obtained. Random sampling of 50% of charts was performed to assess the impact of the ocular history and pretreatment measures. The relationship between probability of negative laboratory results with demographics, ocular history, pretreatment measures, and utilization of a new specimen collection method (i.e. ESwab) was evaluated by multivariable logistic regression. RESULTS: Of 3395 microbial keratitis patients identified, 31% (n = 1051) had laboratory tests. Laboratory testing increased over time (slope = 2.5% per year, p < 0.001; 19.6% in 2013 to 42.2% in 2021). Laboratory negative rate increased over time (slope = 2.2% per year, p = 0.022; 48.5% in 2013 to 62.3% in 2021). Almost one-third of patients (31.2%, n = 164) were pretreated with steroids. Over two-thirds of patients were pretreated with antibiotics (69.5%, n = 367). 56.5% (n = 297) of patients were outside referrals. In multivariable regression, patients with corticosteroid pretreatment had lower odds of negative laboratory results (odds ratio [OR] = 0.49, p = 0.001). There were higher odds of negative laboratory results for every additional antibiotic prescribed to a patient prior to presentation (OR = 1.30, p = 0.006) and for specimens collected using ESwabs (OR = 1.69, p = 0.005). Age, prior eye trauma, outside referrals, and contact lens wear were not significantly associated with negative laboratory results. CONCLUSION: More microbial keratitis associated laboratory tests are being taken over time. Over 60% of tests were negative by 2022. Factors associated with negative laboratory test results included pretreatment with antibiotics and specimens collected with the new collection method.

Donor age and factors related to endothelial cell loss 10 years after penetrating keratoplasty: Specular Microscopy Ancillary Study.

OBJECTIVE: To examine the effect of donor age and other perioperative factors on long-term endothelial cell loss after penetrating keratoplasty (PKP). DESIGN: Multicenter, prospective, double-masked clinical trial. PARTICIPANTS: We included 176 participants from the Cornea Donor Study cohort who had not experienced graft failure ≥ 10 years after PKP for a moderate risk condition (principally Fuchs' dystrophy or pseudophakic/aphakic corneal edema). METHODS: Corneas from donors 12 to 75 years old were assigned to participants using a randomized approach, without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines. Images of the central endothelium were obtained preoperatively and at intervals for 10 years postoperatively. Images were analyzed by a central image analysis reading center to determine endothelial cell density (ECD). MAIN OUTCOME MEASURES: Endothelial cell density at 10 years. RESULTS: Among study participants with a clear graft at 10 years, the 125 who received a cornea from a donor 12 to 65 years old experienced a median cell loss of 76%, resulting in a 10-year median ECD of 628 cells/mm(2) (interquartile range [IQR], 522-850 cells/mm(2)), whereas the 51 who received a cornea from a donor 66 to 75 years old experienced a cell loss of 79%, resulting in a median 10-year ECD of 550 cells/mm(2) (IQR, 483-694 cells/mm(2); P adjusted for baseline ECD = 0.03). In addition to younger donor age, higher ECD values were significantly associated with higher baseline ECD (P<0.001) and larger donor tissue size (P<0.001). Forty-two of the 176 participants (24%) had an ECD of <500 cells/mm(2) at 10 years and only 24 (14%) had an ECD of >1000 cells/mm(2). CONCLUSIONS: Substantial cell loss occurs in eyes with a clear graft 10 years after PKP, with the rate of cell loss being slightly greater with older donor age. Greater preoperative ECD and larger donor tissue size are associated with higher ECD at 10 years.

Femtosecond lasers for LASIK flap creation: a report by the American Academy of Ophthalmology.

OBJECTIVE: To review the published literature to assess the safety, efficacy, and predictability of femtosecond lasers for the creation of corneal flaps for LASIK; to assess the reported outcomes of LASIK when femtosecond lasers are used to create corneal flaps; and to compare the differences in outcomes between femtosecond lasers and mechanical microkeratomes. METHODS: Literature searches of the PubMed and Cochrane Library databases were last conducted on October 12, 2011, without language or date limitations. The searches retrieved a total of 636 references. Of these, panel members selected 58 articles that they considered to be of high or medium clinical relevance, and the panel methodologist rated each article according to the strength of evidence. Four studies were rated as level I evidence, 14 studies were rated as level II evidence, and the remaining studies were rated as level III evidence. RESULTS: The majority of published studies evaluated a single laser platform. Flap reproducibility varied by device and the generation of the device. Standard deviations in flap thicknesses ranged from 4 to 18.4 µm. Visual acuities and complications reported with LASIK flaps created using femtosecond lasers are within Food and Drug Administration safety and efficacy limits. Of all complications, diffuse lamellar keratitis is the most common after surgery but is generally mild and self-limited. Corneal sensation was reported to normalize by 1 year after surgery. Unique complications of femtosecond lasers included transient light-sensitivity syndrome, rainbow glare, opaque bubble layer, epithelial breakthrough of gas bubbles, and gas bubbles within the anterior chamber. CONCLUSIONS: Available evidence (levels I and II) indicates that femtosecond lasers are efficacious devices for creating LASIK flaps, with accompanying good visual results. Overall, femtosecond lasers were found to be as good as or better than mechanical microkeratomes for creating LASIK flaps. There are unique complications that can occur with femtosecond lasers, and long-term follow-up is needed to evaluate the technology fully.

The effect of donor age on penetrating keratoplasty for endothelial disease: graft survival after 10 years in the Cornea Donor Study.

OBJECTIVE: To determine whether the 10-year success rate of penetrating keratoplasty for corneal endothelial disorders is associated with donor age. DESIGN: Multicenter, prospective, double-masked clinical trial. PARTICIPANTS: A total of 1090 participants undergoing penetrating keratoplasty at 80 sites for Fuchs' dystrophy (62%), pseudophakic/aphakic corneal edema (34%), or another corneal endothelial disorder (4%) and followed for up to 12 years. METHODS: Forty-three eye banks provided corneas from donors aged 12 to 75 years, using a randomized approach to assign donor corneas to study participants without respect to recipient factors. Surgery and postoperative care were performed according to the surgeons' usual routines. MAIN OUTCOME MEASURES: Graft failure defined as a regraft or, in the absence of a regraft, a cloudy cornea that was sufficiently opaque to compromise vision for 3 consecutive months. RESULTS: In the primary analysis, the 10-year success rate was 77% for 707 corneas from donors aged 12 to 65 years compared with 71% for 383 donors aged 66 to 75 years (difference, +6%; 95% confidence interval, -1 to +12; P = 0.11). When analyzed as a continuous variable, higher donor age was associated with lower graft success beyond the first 5 years (P<0.001). Exploring this association further, we observed that the 10-year success rate was relatively constant for donors aged 34 to 71 years (75%). The success rate was higher for 80 donors aged 12 to 33 years (96%) and lower for 130 donors aged 72 to 75 years (62%). The relative decrease in the success rate with donor ages 72 to 75 years was not observed until after year 6. CONCLUSIONS: Although the primary analysis did not show a significant difference in 10-year success rates comparing donor ages 12 to 65 years and 66 to 75 years, there was evidence of a donor age effect at the extremes of the age range. Because we observed a fairly constant 10-year success rate for donors aged 34 to 71 years, which account for approximately 75% of corneas in the United States available for transplant, the Cornea Donor Study results indicate that donor age is not an important factor in most penetrating keratoplasties for endothelial disease.

Keratoplasty for corneal endothelial disease, 2001-2009.

PURPOSE: To determine the rates of keratoplasty for corneal endothelial disease (CED) from 2001 to 2009 in a large managed care network in the United States, factors that affect which patients undergo this procedure and surgical outcomes. DESIGN: A retrospective review of data from a longitudinal cohort study. PARTICIPANTS: Beneficiaries with CED aged ≥ 40 years who were receiving eye care during 2001 to 2009. METHODS: Rates of keratoplasty for CED were determined at 6-month intervals from January 2001 to December 2009. The mean number of postoperative visits and rates of severe adverse events in the year after keratoplasty surgery were monitored over the course of the decade. Univariable and multivariable logistic regression were performed to identify sociodemographic and other factors associated with undergoing keratoplasty for CED. MAIN OUTCOME MEASURES: Odds of undergoing keratoplasty with 95% confidence intervals, changes in the number of postoperative visits, and rates of adverse events in the year after keratoplasty. RESULTS: Of the 38 648 enrollees who met the inclusion criteria, 2187 underwent ≥ 1 keratoplasty surgeries from January 2001 to December 2009. After adjustment for confounding factors, individuals with CED had 47% increased odds of undergoing keratoplasty during 2007-2009 relative to 2001-2006. The mean number of postoperative visits to eyecare providers in the year after keratoplasty declined from 12.6 in 2001-2006 to 10.5 in 2007-2008. There was no difference in the proportion of enrollees who developed adverse events after keratoplasty over time. CONCLUSIONS: In this analysis of claims data, from 2001 to 2009, a period during which there was an increase in the rate of endothelial keratoplasty, we observed a trend of greater rates of keratoplasty in patients with CED and fewer visits for postoperative care in the later years of the decade compared with the earlier years, along with no change in rates of severe adverse events.

A Randomized Trial of Topical Fibrinogen-Depleted Human Platelet Lysate Treatment of Dry Eye Secondary to Chronic Graft-versus-Host Disease.

Purpose: The purpose of the study was to evaluate, as a pilot trial, safety and tolerability of CAM-101 10% and 30% topical ophthalmic fibrinogen-depleted human platelet lysate (FD hPL) solution in patients with dry eye disease (DED) secondary to graft-versus-host disease (GvHD) after 6 weeks of treatment. Design: A phase I/II, pilot, prospective, multicenter, randomized, double-masked clinical trial. Participants: Patients with DED secondary to GvHD. Methods: Sixty-four adult patients were stratified by "symptom severity" (Ocular Surface Disease Index [OSDI], ocular discomfort Visual Analog Scale (VAS), ocular symptom frequency, and use of artificial tears) and then randomized 1:1:1 to CAM-101 (FD hPL) at 10% or 30% concentration or an electrolyte (Plasma-Lyte A) vehicle control, 1 drop in both eyes, 4 times daily, for 42 days. After 42 days, control patients were offered 42 days of open-label treatment with 30% FD hPL. Main Outcome Measures: Primary outcome safety measures were ocular and systemic adverse events and the number of patients in each group with clinically significant change from normal to abnormal in any ocular findings. Secondary outcomes were changes from baseline to day 42 in ocular discomfort, OSDI, fluorescein corneal staining, and lissamine green conjunctival staining relative to the vehicle control. The ocular symptom frequency was assessed on a 100-point VAS. Results: FD hPL 10% and 30% were safe and well tolerated. Relative to the vehicle control, significant decreases from baseline to day 42 were seen in the FD hPL 30% group with regard to ocular discomfort (mean decrease = -18.04; P = 0.018), frequency of burning/stinging (-20.23; P = 0.022), eye discomfort (-32.97; P < 0.001), eye dryness (-21.61; P = 0.020), pain (-15.12; P = 0.044), photophobia (-24.33; P = 0.0125), and grittiness (-20.08; P = 0.0185). Decreases were also seen for itching and foreign body sensation, though not statistically significant. Improvements were seen in tear breakup time (mean increase = 1.30 seconds; P = 0.082) and the investigator's global evaluation 4-point scale (mean decrease = -0.86; P = 0.026). Corneal fluorescein staining was not improved. The OSDI had a mean decrease of -8.88 compared to the vehicle, although not statistically significant. Conclusions: Fibrinogen-depleted human platelet lysate appears to be well tolerated, with no significant toxicity at concentrations of 10% and 30%. These initial data suggest some efficacy, especially for subjective outcome measures relative to baseline assessments and treatment with the vehicle, but larger studies are needed to confirm these effects.

Severe adverse events after cataract surgery among medicare beneficiaries.

PURPOSE: To determine rates and risk factors associated with severe postoperative complications after cataract surgery and whether they have been changing over the past decade. DESIGN: Retrospective longitudinal cohort study. PARTICIPANTS: A total of 221 594 Medicare beneficiaries who underwent cataract surgery during 1994-2006. METHODS: Beneficiaries were stratified into 3 cohorts: those who underwent initial cataract surgery during 1994-1995, 1999-2000, or 2005-2006. One-year rates of postoperative severe adverse events (endophthalmitis, suprachoroidal hemorrhage, retinal detachment) were determined for each cohort. Cox regression analyses determined the hazard of developing severe adverse events for each cohort with adjustment for demographic factors, ocular and medical conditions, and surgeon case-mix. MAIN OUTCOME MEASURES: Time period rates of development of severe postoperative adverse events. RESULTS: Among the 221 594 individuals who underwent cataract surgery, 0.5% (1086) had at least 1 severe postoperative complication. After adjustment for confounders, individuals who underwent cataract surgery during 1994-1995 had a 21% increased hazard of being diagnosed with a severe postoperative complication (hazard ratio [HR] 1.21; 95% confidence interval [CI], 1.05-1.41) relative to individuals who underwent cataract surgery during 2005-2006. Those who underwent cataract surgery during 1999-2000 had a 20% increased hazard of experiencing a severe complication (HR 1.20; 95% CI, 1.04-1.39) relative to the 2005-2006 cohort. Risk factors associated with severe adverse events include a prior diagnosis of proliferative diabetic retinopathy (HR 1.62; 95% CI, 1.07-2.45) and cataract surgery combined with another intraocular surgical procedure on the same day (HR 2.51; 95% CI, 2.07-3.04). Individuals receiving surgery by surgeons with the case-mix least prone to developing a severe adverse event (HR 0.52; 95% CI, 0.44-0.62) had a 48% reduced hazard of a severe adverse event relative to recipients of cataract surgery performed by surgeons with the case-mix most prone to developing such outcomes. CONCLUSIONS: Rates of sight-threatening adverse events after cataract surgery declined during 1994-2006. Future efforts should be directed to identifying ways to reduce severe adverse events in high-risk groups.

Phakic intraocular lens implantation for the correction of myopia: a report by the American Academy of Ophthalmology.

OBJECTIVE: To review the published literature for evaluation of the safety and outcomes of phakic intraocular lens (pIOL) implantation for the correction of myopia and myopic astigmatism. METHODS: Literature searches of the PubMed and Cochrane Library databases were conducted on October 7, 2007, and July 14, 2008. The PubMed search was limited to the English language; the Cochrane Library was searched without language limitations. The searches retrieved 261 references. Of these, panel members chose 85 papers that they considered to be of high or medium clinical relevance to this assessment. The panel methodologist rated the articles according to the strength of evidence. RESULTS: Two pIOLs have been approved by the US Food and Drug Administration (FDA): one iris-fixated pIOL and one posterior-chamber IOL. In FDA trials of iris-fixated pIOLs, uncorrected visual acuity (UCVA) was >or=20/40 in 84% and >or=20/20 in 31% after 3 years. In FDA trials of posterior-chamber pIOLs, UCVA was >or=20/40 in 81% and >or=20/20 in 41%. Satisfaction with the quality of vision with both types of pIOLs was generally high. Toric anterior- and posterior-chamber pIOLs have shown improved clinical results in European trials compared with spherical pIOLs. Comparative studies showed pIOLs to provide better best spectacle-corrected visual acuity (BSCVA) and refractive predictability and stability compared with LASIK and photorefractive keratectomy and to have a lower risk of retinal detachment compared with refractive lens exchange. Reported complications and long-term safety concerns include endothelial cell loss, cataract formation, secondary glaucoma (pupillary block, pigment dispersion), iris atrophy (pupil ovalization), and traumatic dislocation. CONCLUSIONS: Phakic IOL implantation is effective in the correction of myopia and myopic astigmatism. In cases of high myopia of -8 diopters or more, pIOLs may provide a better visual outcome than keratorefractive surgeries and better safety than refractive lens exchange. The short-term rates of complications and loss of BSCVA are acceptable. Comprehensive preoperative evaluation and long-term postoperative follow-up examinations are needed to monitor for and prevent serious complications, and to establish long-term safety.

Recipient risk factors for graft failure in the cornea donor study.

PURPOSE: To identify recipient factors that may be related to risk of corneal graft failure. DESIGN: Multicenter, prospective, double-masked, controlled clinical trial. PARTICIPANTS: One thousand ninety subjects undergoing corneal transplantation for a moderate-risk condition (principally Fuchs' dystrophy or pseudophakic corneal edema). METHODS: Donor corneas were assigned using a random approach without respect to recipient factors, and surgeons were masked to information about the donor cornea, including donor age. Surgery and postoperative care were performed according to the surgeons' usual routines, and subjects were followed up for 5 years. Baseline factors were evaluated for their association with graft failure. MAIN OUTCOME MEASURES: Graft failure, defined as a regraft or a cloudy cornea that was sufficiently opaque to compromise vision for a minimum of 3 consecutive months. RESULTS: Preoperative diagnosis of pseudophakic or aphakic corneal edema increased graft failure risk approximately 4-fold compared with Fuchs' dystrophy (27% vs. 7%). Prior glaucoma surgery with preoperative glaucoma medication use substantially increased the graft failure rate. Factors not strongly associated with graft failure included age, gender, diabetes, smoking, and graft size. CONCLUSIONS: The risk of graft failure is significantly increased in eyes with pseudophakic or aphakic corneal edema compared with Fuchs' dystrophy, independent of lens status, and in eyes with a history of glaucoma. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Glaucoma and Cornea Surgery Outcomes in Peters Anomaly.

PURPOSE: To conduct a qualitative description of corneal and glaucoma outcomes in Peters anomaly. DESIGN: Retrospective case series. METHODS: Children with Peters anomaly who presented between 1982-2017 were included. Visual acuity, intraocular pressure (IOP), survival of corneal grafts, and success of glaucoma surgery (defined as IOP of 5-20 mm Hg and no additional IOP-lowering surgery or visually devastating complications) were analyzed. RESULTS: Fifty-eight eyes of 37 patients (19 males) with Peters anomaly presented at 0.7 ± 1.5 years of age and had a follow-up of 10.2 ± 10.8 years. Twenty-three eyes underwent penetrating keratoplasty (PKP) with an average of 2.0 ± 1.3 grafts per eye. PKP survival at 1 year was 60% (95% confidence interval 41-75%) but decreased at 10 years to 34% (95% confidence interval 18-51%). Thirty-four eyes were diagnosed with glaucoma at 2.8 ± 6.4 years of age. Twenty eyes required glaucoma surgery, and the average number of IOP-lowering surgeries was 2.9 ± 2.0 per eye. Glaucoma drainage devices (15 eyes) had a 53% success rate. Laser cycloablation (9 eyes, transcleral or endoscopic) had a success rate of 67% with 2.0 ± 1.0 treatments per eye. Trabeculectomy with mitomycin C (8 eyes) and trabeculotomy (8 eyes) had 25% and 0% success rates, respectively. Fifteen eyes that underwent glaucoma surgery obtained IOP control, and GDD with or without cycloablation accounted for 80% of the successes. Eyes that underwent PKP did not show increased rates of glaucoma, higher IOP, or a greater necessity for IOP-lowering surgery. CONCLUSIONS: In Peters anomaly, PKP shows poor long-term success. In addition, >50% of eyes with Peters anomaly have secondary glaucoma that often requires multiple surgeries.

A Multicenter Study Evaluating the Risk Factors and Outcomes of Repeat Descemet Stripping Endothelial Keratoplasty.

PURPOSE: Descemet stripping endothelial keratoplasty (DSEK), currently the most common procedure for managing corneal endothelial dysfunction, may be repeated following DSEK failure from a variety of causes. This multicenter study reports the risk factors and outcomes of repeat DSEK. METHODS: This was an institutional review board-approved multicenter retrospective chart review of patients who underwent repeat DSEK. Twelve surgeons from 5 Midwest academic centers and 3 private practice groups participated. The Eversight Eye Bank provided clinical indication and donor graft data. We also assessed the role of the learning curve by comparing cohorts from the first and second 5-year periods. RESULTS: A total of 121 eyes from 121 patients who underwent repeat DSEK were identified. The average age of the patients was 70 ± 12 years. The most common indication for repeat DSEK was late endothelial graft failure without rejection (58%, N = 63). Average preoperative and 12-month postoperative repeat DSEK corrected distance visual acuities were 20/694 and 20/89, respectively. Visual acuity outcomes, endothelial cell density, and cell loss did not significantly vary between the 2 cohorts. Initial graft rebubble rates for the first and second cohorts were 51% and 25%. The presence of glaucoma, prior glaucoma surgery, or a history of penetrating (full thickness) keratoplasty did not significantly affect visual outcomes. The median, mean, and range of intraocular pressures before repeat DSEK were 15.0, 15.7, and 6 to 37 mm Hg, respectively. Patients with higher intraocular pressures before repeat DSEK had improved postoperative corrected distance visual acuities. CONCLUSIONS: Repeating DSEK improves vision following failed or decompensated DSEK surgery. Higher preoperative repeat DSEK IOPs were associated with improved visual outcomes, and initial graft rebubble rates, which decreased over time, were likely due to surgeon experience.

Donor, Recipient, and Operative Factors Associated With Increased Endothelial Cell Loss in the Cornea Preservation Time Study.

Importance: Determining factors associated with endothelial cell loss after Descemet stripping automated endothelial keratoplasty (DSAEK) could improve long-term graft survival. Objective: To evaluate the associations of donor, recipient, and operative factors with endothelial cell density (ECD) 3 years after DSAEK in the Cornea Preservation Time Study. Design, Setting, and Participants: This cohort study was a secondary analysis of data collected in a multicenter, double-masked, randomized clinical trial. Forty US clinical sites with 70 surgeons participated, with donor corneas provided by 23 US eye banks. Individuals undergoing DSAEK for Fuchs dystrophy or pseudophakic/aphakic corneal edema were included. Interventions: The DSAEK procedure, with random assignment of a donor cornea with a preservation time of 0 to 7 days or 8 to 14 days. Main Outcomes and Measures: Endothelial cell density at 3 years as determined by a reading center from eye bank and clinical specular or confocal central endothelial images. Results: The study included 1090 participants (median age, 70 years) with 1330 affected eyes (240 bilateral cases [22.0%]), who underwent DSAEK for Fuchs dystrophy (1255 eyes [94.4%]) or pseudophakic/aphakic corneal edema (PACE) (75 eyes [5.6%]). Of these, 801 eyes (60.2%) belonged to women and 1207 (90.8%) to white individuals. A total of 749 participants (913 eyes; 164 [21.9%] bilateral cases) had functioning grafts with acceptable endothelial images preoperatively and at 3 years postoperatively and were included in this analysis. Factors associated with a lower ECD at 3 years (estimated effect with 99% CI) in the final multivariable model included donors with diabetes (-103 [-196 to -9] cells/mm2), lower screening ECD (-234 [-331 to -137] per 500 cells/mm2), recipient diagnosis of PACE (-257 [-483 to -31] in cells/mm2), and operative complications (-324 [-516 to -133] in cells/mm2). Endothelial cell loss (ECL) from a preoperative measurement to a 3-year postoperative measurement was 47% (99% CI, 42%-52%) for participants receiving tissue from donors with diabetes vs 43% (99% CI, 39%-48%) without diabetes; it was 53% (99% CI, 44%-62%) for participants diagnosed with PACE vs 44% (99% CI, 39%-49%) for those diagnosed with Fuchs dystrophy, and 55% (99% CI, 48%-63%) in participants who experienced operative complications vs 44% (99% CI, 39%-48%) in those who did not. No other donor, recipient, or operative factors were significantly associated with 3-year ECD. Conclusions and Relevance: Donor diabetes, lower screening ECD, a PACE diagnosis in the recipient, and operative complications were associated with lower ECD at 3 years after DSAEK surgery and may be associated with long-term graft success. While causation cannot be inferred, further studies on the association of donor diabetes and PACE in recipients with lower 3-year ECD warrant further study.