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1.
Am J Ophthalmol ; 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32171765

RESUMO

PURPOSE: To evaluate the utility of repeat cultures at days 3 and 7 after starting antifungal medications for predicting outcomes in fungal keratitis. DESIGN: Pre-specified secondary analysis of the randomized clinical trial Mycotic Antimicrobial Localized Injection trial. METHODS: Patients presenting to Aravind Eye Hospital, Pondicherry with fungal keratitis and visual acuity worse than 20/70 received topical natamycin and were randomized to either receive intrastromal injection of voriconazole or topical therapy alone. All subjects received corneal cultures at date of presentation, day 3, and day 7. Outcome measures included 3-week and 3-month visual acuity and scar size, corneal perforation and/or the need for therapeutic penetrating keratoplasty (TPK). Visual acuity and scar size were analyzed with multiple linear regression controlling for baseline measures. Survival analysis was used to analyze the risk of corneal perforation and/or need for TPK. RESULTS: Of the 70 study subjects with fungal keratitis, 25/69 (36%) remained culture positive at day 3, and 20/62 (32%) were culture positive at day 7. Culture positivity at day 3 conferred a hazard ratio of 2.8 for requiring TPK (p=0.03), but was not a statistically significant predictor of perforation, scar size, or final visual acuity. Culture positivity at day 7 had a hazard ratio of 3.5 for requiring TPK (p=0.003). Those with positive cultures at day 7 had on average 3-LogMAR lines worse visual acuity at 3 months (95% CI 0.9 to 5.2-LogMAR lines, p=0.006) and 1.1 mm larger scar size at 3 months after controlling for baseline measures (95% CI 0.1 to 2.2 mm; p=0.03). CONCLUSIONS: While not as predictive as day 7 cultures, culture positivity at day 3 after starting treatment is a significant predictor of the need for TPK in patients with moderate to severe filamentous fungal keratitis. This has applications for risk stratification, and may facilitate earlier consideration of TPK in high-risk patients.

2.
Sci Rep ; 10(1): 2395, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32024933

RESUMO

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

3.
Cornea ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31939923

RESUMO

PURPOSE: To compare the degree of corneal light scatter as measured by densitometry in ultrathin Descemet Stripping Automated Endothelial Keratoplasty (UT-DSAEK) and Descemet Membrane Endothelial Keratoplasty (DMEK) in the Descemet endothelial thickness comparison trial. METHODS: This was a prespecified secondary analysis of the Descemet endothelial thickness comparison trial, which was a prospective, randomized controlled trial. Subjects with isolated endothelial dysfunction were enrolled and were randomized to either UT-DSAEK or DMEK. Corneal opacity was quantitatively measured by Pentacam densitometry (OCULUS) at 3, 6, and 12 months. RESULTS: Fifty eyes of 38 patients were enrolled at the Casey Eye Institute at Oregon Health & Science University and the Byers Eye Institute at Stanford University. Corneal densitometry for the anterior and posterior layers improved in both UT-DSAEK and DMEK after surgery. The decrease was more pronounced in the posterior layer for both groups. However, there was no difference in the degree of corneal light scatter between UT-DSAEK and DMEK at postoperative month 12, and no difference in change in densitometry was observed between the 2 arms from baseline to month 12. CONCLUSIONS: Both UT-DSAEK and DMEK experience an improvement in the degree of corneal light scatter after surgery. However, there was no difference in densitometry between the 2 groups at month 12. Therefore, other factors such as higher order aberrations in the posterior cornea rather than stromal-stromal interface haze mediate the superior visual outcomes in DMEK compared with UT-DSAEK.

4.
Ophthalmology ; 127(2): 159-166, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31619359

RESUMO

PURPOSE: To determine if there is a benefit to adjuvant corneal crosslinking (CXL) and to compare natamycin versus amphotericin B for filamentous fungal keratitis. DESIGN: Outcome-masked, 2×2 factorial design, randomized controlled clinical trial. PARTICIPANTS: Consecutive patients presenting with moderate vision loss from a smear-positive fungal ulcer at Aravind Eye Hospital, Madurai, India. METHODS: Study eyes were randomized to 1 of 4 treatment combinations using an adaptive randomization protocol. The treatment arms included (1) topical natamycin 5% alone, (2) topical natamycin 5% plus CXL, (3) topical amphotericin B 0.15% alone, and (4) topical amphotericin 0.15% plus CXL. MAIN OUTCOME MEASURES: The primary outcome of the trial was microbiological cure at 24 hours on repeat culture. Secondary outcomes included best spectacle-corrected visual acuity (BSCVA) at 3 weeks and 3 months, percentage of study participants with epithelial healing at 3 days, 3 weeks, and 3 months, infiltrate or scar size at 3 weeks and 3 months, 3-day smear and culture, and adverse events. RESULTS: Those randomized to CXL regardless of medication (topical natamycin or amphotericin) had 1.32-fold increased odds of 24-hour culture positivity, although this was not statistically significant (95% confidence interval [CI], 0.57-3.06; P = 0.51). We were also unable to find a difference in 24-hour culture positivity between those randomized to amphotericin and those randomized to natamycin when evaluating as a group regardless of whether or not they received CXL (coefficient 1.10; 95% CI, 0.47-2.54; P = 0.84). The BSCVA was approximately 0.22 logarithm of the minimum angle of resolution (logMAR) (2.2 Snellen lines) worse on average at 3 weeks among those receiving CXL regardless of medication (95% CI, -0.04 to 0.40; P = 0.04) and 0.32 logMAR (3.2 Snellen lines) worse visual acuity at 3 months after controlling for baseline visual acuity (95% CI, 0.03-0.54; P = 0.02). There was no difference in infiltrate or scar size, percentage of epithelialized or adverse events when comparing CXL with no CXL or the 2 topical medications. CONCLUSIONS: There appears to be no benefit of adjuvant CXL in the primary treatment of moderate filamentous fungal ulcers, and it may result in decreased visual acuity.

5.
BMJ Open ; 9(12): e033175, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31862739

RESUMO

INTRODUCTION: Cytomegalovirus (CMV) anterior uveitis is a recognised cause of anterior uveitis in immunocompetent patients and is preventable cause of vision loss. Ocular sequelae include corneal endothelial damage which can cause corneal oedema and failure, as well as glaucoma. Recurrences of inflammation are common and therefore patients are often exposed to long-term therapy. Oral therapy is available in the form of valganciclovir, although with the caveat of systemic side effects such as bone marrow suppression and renal failure necessitating regular interval laboratory monitoring. Recent reports have demonstrated that topical 2% ganciclovir solution may offer promising treatment outcomes in patients with CMV anterior uveitis with superior safety, cost-effectiveness and convenience profiles. An investigation into the relative equipoise of these therapies is warranted for these reasons. METHODS AND ANALYSIS: The Systemic and Topical Control of Cytomegalovirus Anterior uveitis: Treatment Outcomes (STACCATO) trial is designed as a multicentre, block randomised by site, double-masked, placebo-controlled trial comparing the efficacy of oral valganciclovir, 2% topical ganciclovir and placebo in treating PCR-proven CMV anterior uveitis. Participant clinical evaluation will occur at three study time points by a masked study ophthalmologist over a 28-day period to assess resolution of ocular inflammation (secondary outcome). A control group will provide additional information about the possible impact that the infected host's immune response may play in controlling local viral replication. The primary analysis is an analysis of covariance (three arms) correcting for baseline to compare quantitative CMV viral load in the anterior chamber (AC) aqueous fluid before and 7 days after treatment. ETHICS AND DISSEMINATION: The University of California San Francisco Committee on Human Research and the Khon Kaen University Institutional Review Board have given ethical approval. The results of this trial will be presented at local and international meetings and submitted for peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER: NCT03576898.

6.
Cornea ; 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31725701

RESUMO

PURPOSE: To report the clinical characteristics and outcomes of pediatric patients with keratoconus (KCN) who underwent corneal collagen cross-linking (CXL) under general anesthesia for developmental delay or inability to cooperate with topical anesthesia. METHODS: In this retrospective case series, we reviewed the medical charts of pediatric patients with KCN who had CXL under general anesthesia from January 2018 to April 2019. Baseline disease characteristics of patients with and without developmental delay were compared using the Pearson χ test and the t test. Main outcomes were anesthesia or surgical complications and postoperative best corrected visual acuity (BCVA), keratometry (K) values, and caregiver report of eye-rubbing behavior. RESULTS: Fourteen eyes of 9 patients were reviewed. All were habitual eye rubbers at baseline. Six (66.7%) were developmentally delayed. Compared with patients without developmental delay, developmentally delayed patients were diagnosed and treated at older ages (16.0 vs. 13.9 years), experienced longer delays from diagnosis to surgery (20.7 vs. 8.8 weeks), and had lower BCVA (20/70 vs. 20/40), higher steep K values (54.0 vs. 50.9), and a higher incidence of corneal scarring (75.0% vs. 33.3%) and monocular vision loss (50.0% vs. 0.0%) at baseline, although these differences were not statistically significant. No anesthesia or surgical complications occurred. BCVA and K values were stable at postoperative month 6, with no clinically or statistically significant change observed for either measure. Eight patients decreased or stopped eye rubbing. CONCLUSIONS: We demonstrate the efficacy and safety of CXL under general anesthesia in halting the progression of KCN for pediatric patients with developmental delay or an inability to cooperate with the procedure until topical anesthesia.

7.
Sci Rep ; 9(1): 16385, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705138

RESUMO

Homeostatic maintenance of corneal endothelial cells is essential for maintenance of corneal deturgescence and transparency. In Fuchs endothelial corneal dystrophy (FECD), an accelerated loss and dysfunction of endothelial cells leads to progressively severe visual impairment. An abnormal accumulation of extracellular matrix (ECM) is a distinctive hallmark of the disease, however the molecular pathogenic mechanisms underlying this phenomenon are not fully understood. Here, we investigate genome-wide and sequence-specific DNA methylation changes of miRNA genes in corneal endothelial samples from FECD patients. We discover that miRNA gene promoters are frequent targets of aberrant DNA methylation in FECD. More specifically, miR-199B is extensively hypermethylated and its mature transcript miR-199b-5p was previously found to be almost completely silenced in FECD. Furthermore, we find that miR-199b-5p directly and negatively regulates Snai1 and ZEB1, two zinc finger transcription factors that lead to increased ECM deposition in FECD. Taken together, these findings suggest a novel epigenetic regulatory mechanism of matrix protein production by corneal endothelial cells in which miR-199B hypermethylation leads to miR-199b-5p downregulation and thereby the increased expression of its target genes, including Snai1 and ZEB1. Our results support miR-199b-5p as a potential therapeutic target to prevent or slow down the progression of FECD disease.

8.
9.
Indian J Ophthalmol ; 67(10): 1593-1598, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31546487

RESUMO

Purpose: To understand demographic and socioeconomic barriers and treatment-seeking behaviors of patients with infectious keratitis requiring therapeutic penetrating keratoplasty (TPK) in a developing country. Methods: This prospective non-comparative questionnaire- based study included all patients presenting to Aravind Eye Hospital, Madurai with infectious keratitis that eventuated to TPK between November 2015 and October 2016. A structured questionnaire was administered on post-operative day 3 to collect data on the demographic details, predisposing factors, prior treatment received, and treatment expenditures. Results: In total, 227 patients underwent TPK between November 2015 and October 2016 for infectious keratitis. The majority of patients were males (n = 132, 58.1%), illiterate (n = 129, 56.8%), and had a family monthly income of less than INR 6000 (n = 142, 62.5%). Most of the patients (n = 163, 71.8%) had prior treatment with an ophthalmologist before presenting to our hospital. The mean distance travelled to reach our centre was 269.2 ± 298.5 km. The mean duration of disease before the presentation was 20.3 ± 21.1 days. Corneal smear was positive for fungus in 163 (88.1%) and Aspergillus was the most commonly isolated fungi in 55 (41.3%) cultures. The mean total cost of treatment was INR 8752.87 ± 7615.39 per patient. There was a positive correlation between the duration of the disease (rho 0.19, P = 0.0034) and the costs of treatment (rho 0.2, P = 0.0024) with the distance travelled by the patient. Conclusion: Patients who travelled a farther distance had a delayed onset of presentation and spent significantly more than their respective counterparts.

10.
Am J Ophthalmol Case Rep ; 15: 100469, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31193794

RESUMO

Purpose: To report two cases of neurotrophic keratitis (NK) after micropulse transscleral cyclophotocoagulation (MP-TCP). Observations: Two patients with predisposing factors for decreased corneal sensation developed NK 1 month after MP-TCP. Both patients did not heal with initial treatment with topical antibiotic and preservative free artificial tears. One patient required use of a bandage contact lens and the other patient required tarsorrhaphy. Both eyes experienced recurrence of NK. Conclusions and importance: NK can be triggered after MP-TCP in patients with underlying predisposing factors for decreased corneal sensation. This uncommon but vision-threatening complication should be discussed preoperatively with high-risk patients as a possible adverse event after MP-TCP and followed closely postoperatively.

11.
JAMA Ophthalmol ; 137(7): 747-754, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31046075

RESUMO

Importance: Vision-related quality of life can be a valuable outcome for some interventions in ophthalmology. In the primary Descemet Endothelial Thickness Comparison Trial (DETECT), Descemet membrane endothelial keratoplasty (DMEK) had superior postoperative visual acuity compared with ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK). It is of interest to determine whether this trend extends to quality of life. Objective: To determine the effect of UT-DSAEK and DMEK on vision-related quality of life. Design, Setting, and Participants: A prespecified secondary analysis of a 2-surgeon patient- and outcome-masked randomized clinical trial was conducted at the Casey Eye Institute in Portland, Oregon, and Byers Eye Institute in Palo Alto, California. The study was conducted between January 20, 2015, and April 26, 2017. DETECT enrolled 38 individuals and included 50 eyes with isolated endothelial dysfunction; for this analysis, the second eye from a single participant was excluded along with any questionnaires in the first eye after second eye surgery for evaluation of 38 eyes at baseline and 3 months and 26 eyes at 12 months. Mean (SD) baseline visual acuity was 0.35 (0.31) logMAR in the DMEK arm and 0.28 (0.22) logMAR in the UT-DSAEK arm. Each arm consisted of 19 participants: 18 individuals with Fuchs dystrophy and 1 participant with pseudophakic bullous keratopathy. Interventions: Study eyes were randomized to receive either UT-DSAEK or DMEK. Main Outcomes and Measures: Responses to the National Eye Institute (NEI) Visual Function Questionnaire-39 (VFQ-39) administered at baseline and 3 and 12 months postoperatively were analyzed using the NEI-defined traditional subscales and composite score on a 100-point scale and with a Rasch-refined analysis. Results: There were more women in both arms of the study (UT-DSAEK, 12 [63%]; DMEK, 11 [58%]); mean (SD) age was 68 (11) years in the UT-DSAEK arm and 68 (4) years in the DMEK arm. Overall, study participants experienced a 9.1-point improvement in NEI VFQ-39 composite score at 3 months compared with baseline (N = 38; 95% CI, 4.9-13.3; P < .001), and an 11.6-point improvement at 12 months compared with baseline (n = 26; 95% CI, 6.8-16.4; P < .001). Eyes randomized to DMEK had 0.9 points more improvement in NEI VFQ-39 composite score at 3 months compared with UT-DSAEK after controlling for baseline NEI VFQ-39 (95% CI, -6.2 to 8.0; P = .80). Conclusions and Relevance: Improvement in vision-related quality of life was not shown to be greater with DMEK compared with UT-DSAEK. Trial Registration: ClinicalTrials.gov identifier: NCT02373137.


Assuntos
Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Epitélio Posterior/patologia , Distrofia Endotelial de Fuchs/cirurgia , Qualidade de Vida/psicologia , Acuidade Visual/fisiologia , Idoso , Contagem de Células , Método Duplo-Cego , Feminino , Distrofia Endotelial de Fuchs/fisiopatologia , Distrofia Endotelial de Fuchs/psicologia , Sobrevivência de Enxerto/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Perfil de Impacto da Doença , Inquéritos e Questionários
12.
Invest Ophthalmol Vis Sci ; 60(5): 1734-1747, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31022731

RESUMO

Purpose: Matrix metalloproteinases (MMPs) comprise a family of zinc-dependent endopeptidases involved in wound healing processes, including neovascularization and fibrosis. We assessed MMP protein expression levels in diseased corneas of patients requiring penetrating and deep anterior lamellar keratoplasty. The purpose of this study was to test the hypothesis that upregulation of MMPs in diseased corneas is positively associated with clinical levels of corneal neovascularization and fibrosis. Methods: Protein expression levels of nine individual MMPs were quantified simultaneously in human corneal lysates by using the Bio-Plex Pro Human MMP 9-Plex Panel and the MAGPIX technology. Measurements of MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP10, MMP12, and MMP13 were performed on diseased specimens from 21 patients undergoing corneal transplantation (17 for penetrating keratoplasty and 4 for deep anterior lamellar keratoplasty) and 6 normal control corneas. Results: Luminex-based expression analysis revealed a significant overexpression of four of the nine MMPs tested (MMP2, MMP8, MMP12, and MMP13) in patient samples compared to control. Significant overexpression of MMP1, MMP2, MMP8, MMP12, and MMP13 was observed in diseased corneas with neovascularization compared with diseased corneas without neovascularization. Overexpression of MMP1, MMP2, MMP8, MMP12, and MMP13 also corresponded with the levels of corneal fibrosis. Finally, reduced expression of MMP3 was detected in keratoconus patients. Conclusions: Multiple MMPs are expressed in the corneas of patients with chronic disease requiring keratoplasty even when the pathologic process appears to be clinically inactive. In particular, the expression of several MMPs (MMP2, MMP8, MMP12, and MMP13) is positively associated with increased levels corneal fibrosis and neovascularization.


Assuntos
Doenças da Córnea/enzimologia , Doenças da Córnea/cirurgia , Ceratoplastia Penetrante , Metaloproteinases da Matriz/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Córnea/enzimologia , Córnea/patologia , Neovascularização da Córnea/enzimologia , Transplante de Córnea , Feminino , Fibrose/enzimologia , Humanos , Imunoensaio/métodos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
Ophthalmic Epidemiol ; 26(4): 251-256, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31018742

RESUMO

Purpose: To determine the repeatability and reproducibility of anterior segment optical coherence tomography (AS-OCT) and Scheimpflug photography for several measurements of corneal scars, including scar size, scar depth, and corneal thickness. Methods: A series of patients treated for fungal keratitis at a tertiary eye care center in South India were recalled two years after successful treatment. Eyes with corneal scars had a slit lamp examination performed by two ophthalmologists masked to the other's examination. For AS-OCT and Scheimpflug photography, each eye had two scans taken by one technician and a third scan taken by a separate technician. Scar measurements were subsequently assessed from AS-OCT images by three graders masked to each other's results. Repeatability and reproducibility were assessed by calculating the intra-class correlation coefficient (ICC) from mixed effects linear regression models. Results: Fifty eyes had all measurements taken. The corneal scar size, measured as the geometric mean of the two longest perpendicular meridians, ranged from 0.8 to 5.4 (mean 2.8 mm, 95%CI 2.6 to 3.1). Scar size measurements taken by two separate individuals were most reproducible when the border of the scar was traced from the OCT (ICC 0.90, 95%CI 0.86 to 0.94), and least repeatable when assessed from slit lamp examination (ICC 0.80, 95%CI 0.70 to 0.90). Conclusions: AS-OCT and Scheimpflug imaging of corneal scars produced measurements with acceptable reproducibility that could be useful as cornea-specific outcomes for clinical trials.


Assuntos
Cicatriz/diagnóstico , Córnea/patologia , Paquimetria Corneana/métodos , Úlcera da Córnea/complicações , Infecções Oculares Fúngicas/complicações , Microscopia com Lâmpada de Fenda/métodos , Tomografia de Coerência Óptica/métodos , Adulto , Antifúngicos/uso terapêutico , Cicatriz/etiologia , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/tratamento farmacológico , Infecções Oculares Fúngicas/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes
14.
Ophthalmology ; 126(8): 1084-1089, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30904540

RESUMO

PURPOSE: To determine if there is a benefit to adjuvant intrastromal voriconazole (ISV) injections for primary treatment of filamentous fungal keratitis. DESIGN: Outcome-masked, randomized controlled clinical trial. PARTICIPANTS: Patients with moderate vision loss resulting from a smear-positive fungal ulcer. METHODS: Study eyes were randomized to topical natamycin plus ISV injection versus topical natamycin alone. MAIN OUTCOME MEASURES: The primary outcome of the trial was microbiological cure on 3-day repeat culture analysis. Secondary outcomes included microbiological cure on 7-day repeat culture analysis; 3-week and 3-month best spectacle-corrected visual acuity; infiltrate or scar size or both; rate of perforation; therapeutic penetrating keratoplasty (TPK); and other adverse events. RESULTS: A total of 151 patients with smear-positive ulcers were screened and 70 were enrolled at Aravind Eye Hospital, Pondicherry, India. Baseline cultures grew Fusarium in 19 samples (27%), Aspergillus in 17 samples (24%), and other filamentous fungi in 19 samples (27%) and showed negative results in 13 samples (19%). Those randomized to ISV injection had 1.82 times the odds of 3-day culture positivity after controlling for baseline culture status (95% confidence interval [CI], 0.65-5.23; P = 0.26, bias-corrected logistic regression) and 1.98 times the odds of positive 7-day culture results, after controlling for baseline culture status (95% CI, 0.69-5.91; P = 0.20, bias-corrected logistic regression). Those randomized to ISV injection showed 0.5 logMAR lines (approximately 0.5 Snellen lines) of decreased visual acuity (95% CI, -2.6 to 3.6 lines; P = 0.75) and 0.55 mm worse infiltrate or scar size or both at 3 months after controlling for baseline values (95% CI, -0.13 to 1.25; P = 0.11). Intrastromal voriconazole injections showed a 2.85-fold increased hazard of perforation after controlling for baseline infiltrate depth (95% CI, 0.76-10.75; P = 0.12) but no difference in the rate of TPK (hazard ratio, 0.95; 95% CI, 0.44-2.04; P = 0.90). CONCLUSIONS: There seems to be no benefit to adding ISV injections to topical natamycin in the primary treatment of moderate to severe filamentous fungal ulcers. Studies consistently suggest that voriconazole has a limited role in the treatment of filamentous fungal ulcers.

15.
Ophthalmology ; 126(7): 946-957, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30776384

RESUMO

PURPOSE: To compare corneal higher-order aberrations (HOA) after ultrathin Descemet stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK). DESIGN: Patient- and outcome-masked randomized controlled clinical trial. PARTICIPANTS: Patients with damaged or diseased endothelium from Fuchs endothelial dystrophy or pseudophakic bullous keratopathy who were good candidates for DMEK or ultrathin DSAEK. METHODS: Corneal anterior and posterior surface HOA were measured with Scheimpflug imaging before surgery and at 3, 6, and 12 months after surgery. HOA after ultrathin DSAEK and DMEK were compared; correlation was performed between best spectacle-corrected visual acuity (BSCVA) and HOA at each time point. MAIN OUTCOME MEASURES: Higher-order aberrations of the anterior and posterior cornea, expressed as the root mean square deviation from a best fit sphere reference surface. RESULTS: At 3, 6, and 12 months after surgery, the posterior corneal surface had significantly less coma (P ≤ 0.003) and total HOA (P ≤ 0.001) in DMEK compared with ultrathin DSAEK (4.0- and 6.0-mm OZ). Posterior trefoil (P ≤ 0.034), secondary astigmatism (P ≤ 0.042), and tetrafoil (P ≤ 0.045) were lower in DMEK than ultrathin DSAEK at 3, 6, or 12 months (either 4.0- or 6.0-mm OZ). There were no significant differences in anterior surface HOA between DMEK and ultrathin DSAEK at any post-surgical time. Compared with baseline, total posterior HOA was increased (P ≤ 0.036) in ultrathin DSAEK at 3, 6, and 12 months, in contrast to DMEK, where it was decreased (P ≤ 0.044) at 6 and 12 months (4.0- or 6.0-mm OZ, or both). At 6 and 12 months, posterior corneal total HOA correlated with BSCVA (ρ ≤ 0.635, P ≤ 0.001; 4.0- and 6.0-mm OZ). There were no moderate or strong correlations between anterior or combined corneal surface HOA at any time point after surgery. CONCLUSIONS: Descemet membrane endothelial keratoplasty results in less posterior corneal HOA compared with ultrathin DSAEK. Descemet membrane endothelial keratoplasty decreases and ultrathin DSAEK increases posterior corneal HOA compared with presurgical values. Total posterior corneal HOA correlates with 6- and 12-month postoperative visual acuity and may account for the better visual acuity observed after DMEK.

16.
Ophthalmology ; 126(1): 19-26, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29945801

RESUMO

PURPOSE: To compare clinical outcomes of ultrathin Descemet stripping automated endothelial keratoplasty (UT-DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) in the treatment of corneal endothelial dysfunction. DESIGN: Patient and outcome-masked, randomized controlled clinical trial. PARTICIPANTS: Patients with damaged or diseased endothelium from Fuchs endothelial dystrophy or pseudophakic bullous keratopathy who were considered good candidates for DMEK or UT-DSAEK. METHODS: Study eyes were randomized by the eye bank to UT-DSAEK or DMEK 1 to 2 days before surgery. MAIN OUTCOME MEASURES: The primary outcome of the trial was best spectacle-corrected visual acuity (BSCVA) at 6 months. Secondary outcomes included 3- and 12-month BSCVA; 3-, 6-, and 12-month endothelial cell counts; intraoperative and postoperative complications; and change in pachymetry. RESULTS: A total of 216 patients with endothelial dysfunction were screened, and 50 eyes of 38 patients were enrolled by 2 surgeons at Casey Eye Institute at Oregon Health & Science University in Portland, Oregon, and at Byers Eye Institute at Stanford University in Palo Alto, California. Overall, we found DMEK to have better visual acuity outcomes compared with UT-DSAEK after correcting for baseline visual acuity: compared with UT-DSAEK, those randomized to DMEK had 1.5 lines better BSCVA at 3 months (95% confidence interval [CI], 2.5-0.6 lines better; P = 0.002), 1.8 lines better BSCVA at 6 months (95% CI, 2.8-1.0 lines better; P < 0.001), and 1.4 lines better BSCVA at 12 months (95% CI, 2.2-0.7 lines better; P < 0.001). Average endothelial cell counts were 1963 cells/mm2 in DMEK and 2113 cells/mm2 in UT-DSAEK at 6 months (P = 0.17) and 1855 cells/mm2 in DMEK and 2070 cells/mm2 in UT-DSAEK at 12 months (P = 0.051). Intraoperative and postoperative complication rates were similar between groups. CONCLUSIONS: Descemet membrane endothelial keratoplasty had superior visual acuity results compared with UT-DSAEK at 3, 6, and 12 months in patients with isolated endothelial dysfunction with similar complication rates.


Assuntos
Distrofias Hereditárias da Córnea/cirurgia , Lâmina Limitante Posterior/patologia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Distrofia Endotelial de Fuchs/cirurgia , Acuidade Visual/fisiologia , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Distrofias Hereditárias da Córnea/fisiopatologia , Paquimetria Corneana , Método Duplo-Cego , Feminino , Seguimentos , Distrofia Endotelial de Fuchs/fisiopatologia , Humanos , Complicações Intraoperatórias , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Complicações Pós-Operatórias
17.
JAMA Ophthalmol ; 137(2): 185-193, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30422157

RESUMO

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.


Assuntos
Córnea , Perda de Células Endoteliais da Córnea/diagnóstico , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Preservação de Órgãos/métodos , Doadores de Tecidos , Transplantados , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células , Criança , Edema da Córnea/cirurgia , Método Duplo-Cego , Epitélio Posterior/patologia , Feminino , Distrofia Endotelial de Fuchs/cirurgia , Sobrevivência de Enxerto/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Estudos de Tempo e Movimento
18.
Am J Ophthalmol ; 196: 197-207, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30308200

RESUMO

PURPOSE: To identify factors related to graft rejection following Descemet stripping automated endothelial keratoplasty (DSAEK) in the Cornea Preservation Time Study (CPTS). DESIGN: Cohort study within a multicenter randomized clinical trial. METHODS: A total of 1330 eyes of 1090 subjects undergoing DSAEK were randomized to receive a donor cornea with preservation time (PT) of 0-7 days (n = 675) or 8-14 days (n = 655) and followed for 3 years. Central endothelial cell density (ECD) was determined by a central image analysis reading center. Multivariable Cox models adjusted for PT, recipient diagnosis, and surgeon effect were used to identify factors associated with rejection. RESULTS: Cumulative probability of definite graft rejection was 3.6% (99% confidence interval 2.5%-5.3%). Younger recipient age was associated with graft rejection (P < .001; hazard ratio: 0.53 [0.33, 0.83] per decade). PT, donor-recipient sex mismatch, recipient diagnosis, recipient race, graft size, discontinuation of topical corticosteroids and immune-modulators, prior immunizations within 3 months, and prior glaucoma surgery were not associated with rejection (P > .01). Among clear grafts with an ECD measurement at baseline and 3 years (n = 913), endothelial cell loss (ECL) was greater in eyes that experienced a rejection episode (n = 27) than in those that did not (n = 886) (48% vs 38%, P = .03). Twelve of 44 eyes (27%) with definite graft rejection subsequently failed, comprising 15% of the 79 failures in the CPTS. CONCLUSIONS: Graft rejection is uncommon after DSAEK and more likely with younger age, in a study cohort mostly > 50 years old. Rejection increases ECL, but it is not a leading cause of DSAEK failure.


Assuntos
Doenças da Córnea/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Rejeição de Enxerto , Preservação de Órgãos/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo
19.
Ophthalmology ; 125(11): 1700-1709, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30098353

RESUMO

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.


Assuntos
Edema da Córnea/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Distrofia Endotelial de Fuchs/cirurgia , Sobrevivência de Enxerto/fisiologia , Preservação de Órgãos , Doadores de Tecidos , Transplantados , Adulto , Idoso , Contagem de Células , Estudos de Coortes , Edema da Córnea/fisiopatologia , Método Duplo-Cego , Epitélio Posterior/citologia , Bancos de Olhos , Feminino , Distrofia Endotelial de Fuchs/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Fatores de Tempo , Estudos de Tempo e Movimento , Acuidade Visual/fisiologia
20.
Ophthalmic Epidemiol ; 25(4): 315-322, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29718751

RESUMO

PURPOSE: We compare results from regression discontinuity (RD) analysis to primary results of a randomized controlled trial (RCT) utilizing data from two contemporaneous RCTs for treatment of fungal corneal ulcers. METHODS: Patients were enrolled in the Mycotic Ulcer Treatment Trials I and II (MUTT I & MUTT II) based on baseline visual acuity: patients with acuity ≤ 20/400 (logMAR 1.3) enrolled in MUTT I, and >20/400 in MUTT II. MUTT I investigated the effect of topical natamycin versus voriconazole on best spectacle-corrected visual acuity. MUTT II investigated the effect of topical voriconazole plus placebo versus topical voriconazole plus oral voriconazole. We compared the RD estimate (natamycin arm of MUTT I [N = 162] versus placebo arm of MUTT II [N = 54]) to the RCT estimate from MUTT I (topical natamycin [N = 162] versus topical voriconazole [N = 161]). RESULTS: In the RD, patients receiving natamycin had mean improvement of 4-lines of visual acuity at 3 months (logMAR -0.39, 95% CI: -0.61, -0.17) compared to topical voriconazole plus placebo, and 2-lines in the RCT (logMAR -0.18, 95% CI: -0.30, -0.05) compared to topical voriconazole. CONCLUSIONS: The RD and RCT estimates were similar, although the RD design overestimated effects compared to the RCT.


Assuntos
Córnea/microbiologia , Úlcera da Córnea/tratamento farmacológico , Infecções Oculares Fúngicas/tratamento farmacológico , Acuidade Visual , Voriconazol/administração & dosagem , Administração Oral , Idoso , Antifúngicos/administração & dosagem , Úlcera da Córnea/microbiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Infecções Oculares Fúngicas/microbiologia , Feminino , Seguimentos , Fungos/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Soluções Oftálmicas , Resultado do Tratamento
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