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PURPOSE: To examine the frequency of recurrence and identify risk factors for recurrence in patients with acute anterior uveitis (AAU). DESIGN: Retrospective cohort study from a single tertiary ophthalmic clinical center. PARTICIPANTS: All subjects with AAU identified from a database of Inflammatory Eye Disease presenting to Te Whatu Ora (Auckland, New Zealand) between 2008 and 2021. METHODS: Data were collected retrospectively from chart review and electronic patient records for all patients during the study period. Rates of recurrence were reported using the Kaplan-Meier estimator. Multivariate analysis of risk factors for recurrence was calculated using a marginal Cox regression model. MAIN OUTCOME MEASURES: The primary outcome measure was disease recurrence. Secondary outcome measure was moderate vision loss (≤20/50). RESULTS: A total of 2763 eyes of 2092 subjects with AAU were studied, with a median follow-up time of 8.9 years and a total follow-up of 19 794.9 eye-years. Recurrence occurred in the ipsilateral eye in 1258 eyes (45.5%) and in the contralateral eye in 522 eyes (27.3%). Rates of ipsilateral recurrence over 10 years were 38.1% for idiopathic disease, 43.2% for human leukocyte antigen B27 (HLA-B27)/inflammatory arthritis, and 44.9% for viral uveitis. On multivariate analysis, the following were associated with increased risk of ipsilateral recurrence: older age (P < 0.001), Maori ethnicity (P = 0.006), Asian ethnicity (P < 0.001), HLA-B27/inflammatory arthritis (P < 0.001), and viral uveitis (P = 0.018). There was no association with gender, smoking, bilateral disease, or hypertensive uveitis. Rates of contralateral eye involvement were significantly lower than ipsilateral eye recurrence. Contralateral recurrence at 10 years was 15.2% in idiopathic uveitis, 37.6% in HLA-B27/inflammatory arthritis, and 2.0% in viral uveitis. Risk factors identified for contralateral eye involvement were Maori ethnicity (P = 0.003), Pasifika (Pacific Islanders) ethnicity (P = 0.021), and HLA-B27/inflammatory arthritis (P < 0.001). Moderate vision loss (≤20/50) was present in 411 eyes (14.9%) at final follow-up and was more common if time to first recurrence was shorter (P < 0.001). CONCLUSIONS: Approximately half of patients with AAU will develop recurrence in the ipsilateral eye, and one-quarter will have recurrence in the contralateral eye. Patients with viral disease have the highest risk of ipsilateral recurrence and lowest risk of contralateral recurrence. Patients with risk factors for recurrence should be managed and counseled appropriately to minimize the risk of visual loss and complications of uveitis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
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PURPOSE: To identify rates of uveitis reactivation both before and after the coronavirus disease (COVID) 2019 vaccine in subjects with a previous diagnosis of uveitis. DESIGN: Retrospective study. PARTICIPANTS: Subjects were identified from the Inflammatory Eye Disease Registry at Auckland District Health Board diagnosed with uveitis between January 1, 2010, and December 31, 2020. METHODS: Date of COVID vaccination was determined from the patient clinical record. Rate of flare was calculated for 3 months before vaccination and 3 months after each vaccination. MAIN OUTCOME MEASURE: Uveitis flare was defined as the presence of new uveitis activity or increased activity that required a change in uveitis treatment. RESULTS: A total of 4184 eyes of 3008 patients were included in the study with a total of 8474 vaccinations given during the study period. Median age was 54.8 years, and 1474 (49.0%) were female. Noninfectious etiology was most common, occurring in 2296 patients (76.3%) and infectious etiology occurring in 712 patients (23.7%). Rate of uveitis flare was 12.3 per 1000 patient-months at baseline, 20.7 after the first dose, 15.0 after the second dose, 12.8 after the third dose, and 23.9 after the fourth dose. The median period of quiescence before flare was 3.9 years. An increase in uveitis flare was seen in both infectious uveitis (baseline 13.1 compared with 20.2 after first dose, 154% increase) and noninfectious uveitis (baseline 12.4 compared with 20.9 after first dose, 169% increase). Risk factors for uveitis flare were identified to be recurrent uveitis, chronic uveitis, shorter period of quiescence, and first dose of vaccine. Median time to uveitis flare was 0.53 months after the first vaccination, 1.74 months after the second vaccination, and 1.35 months after the third vaccination. CONCLUSIONS: The current study demonstrates an increased risk of uveitis flare after the first dose of COVID vaccination. This risk was highest in those with previous recurrences, chronic uveitis, and shorter period of quiescence. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.
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COVID-19 , Coronavirus , Uveíte , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/complicações , Uveíte/diagnóstico , Uveíte/epidemiologia , Uveíte/etiologia , Vacinação/efeitos adversosRESUMO
BACKGROUND: Few studies have evaluated corneal crosslinking (CXL) in a prospective, randomised fashion. This study aimed to determine the efficacy and safety of CXL to reduce the progression of keratoconus. METHODS: Prospective, unmasked, randomised, contralateral eye controlled trial at a tertiary eye centre. PARTICIPANTS: Individuals with bilateral progressive keratoconus. One eye from each subject was randomised to CXL and the contralateral, untreated eye acted as the control. PRIMARY OUTCOME MEASURE: change in maximum keratometry. SECONDARY OUTCOME MEASURES: uncorrected distance visual acuity, spectacle corrected distance visual acuity, spherical equivalent refraction, simulated keratometry, corneal astigmatism, minimum pachymetry and complications. RESULTS: Thirty-eight individuals (mean age 21.1 ± 6.7 years) were enrolled with one eye treated with CXL. At 5 years, there was a mean decrease in maximum keratometry of treated eyes (-1.45 ± 2.25 D) compared to an increase among the controls (1.71 ± 2.46 D; p < 0.001). There were significant differences between the treated and control groups in the mean change of Steep SimK (-1.07 ± 1.22 vs. 0.96 ± 1.97 D; p < 0.001), Flat SimK (-0.61 ± 1.34 vs. 0.43 ± 1.12 D; p < 0.001), corneal astigmatism (-0.45 ± 1.31 vs. 0.63 ± 1.52 D; p < 0.01) and minimum pachymetry (-32.49 ± 26.32 vs. -13.57 ± 24.11 µm; p < 0.01). Complications included sterile infiltrates (n = 2), microbial keratitis (n = 1), persistent corneal haze/scarring at 5 years (n = 4) and loss of ≥2 lines of corrected distance visual acuity (n = 3). CONCLUSIONS: CXL is an effective and relatively safe intervention to halt or reduce the progression of keratoconus in the majority of eyes for at least 5 years.
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Ceratocone , Adolescente , Adulto , Colágeno , Paquimetria Corneana , Topografia da Córnea , Reagentes de Ligações Cruzadas , Humanos , Ceratocone/diagnóstico , Ceratocone/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Prospectivos , Riboflavina/uso terapêutico , Adulto JovemRESUMO
PURPOSE: To analyze corneal haze after corneal collagen crosslinking (CXL) for progressive keratoconus using Scheimpflug densitometry. SETTING: Auckland District Health Board, Auckland, New Zealand. DESIGN: Prospective randomized controlled study. METHODS: Both eyes of all patients were examined preoperatively and 1, 3, 6, and 12 months postoperatively. One eye of each patient was treated with corneal CXL, with the contralateral eye serving as the control. Examinations included uncorrected distance visual acuity and corrected distance visual acuity (CDVA), slitlamp biomicroscopy, and Scheimpflug tomography (Pentacam). RESULTS: Thirty-six eyes of 36 patients were enrolled. The mean preoperative corneal densitometry was 19.0 ± 3.2 (SD). Postoperatively, the mean densitometry peaked at 1 month, decreasing to baseline level after 6 months without application of topical corticosteroids. The development of haze was significant compared with the contralateral untreated eyes (P < .01). The anterior (120 µm) and inner (central 0.0 to 2.0 mm) zones of the cornea had the highest densitometry after treatment. Lower preoperative central corneal thickness (CCT) was significantly correlated with higher corneal densitometry (P = .03). However, the preoperative CCT, keratometry, and astigmatism did not influence the difference in densitometry between the treated eyes and untreated eyes. There was no evidence of a relationship between densitometry and CDVA (P = .30). CONCLUSIONS: After corneal CXL, patients with keratoconus developed transient corneal haze in the anterior central cornea that might not require specific treatment. Thin corneas were associated with higher densitometry; thus, there might be a greater expectancy of corneal haze in patients with advanced keratoconus. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.
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Colágeno/química , Reagentes de Ligações Cruzadas/uso terapêutico , Ceratocone/terapia , Substância Própria , Topografia da Córnea , Humanos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Estudos Prospectivos , Riboflavina , Raios UltravioletaRESUMO
PURPOSE: Mutations in the zinc finger protein gene ZNF469 cause recessive brittle cornea syndrome, characterized by spontaneous corneal perforations. Genome-wide association studies (GWAS) have implicated common variants in this gene as a determinant for central corneal thickness (CCT). We investigated the contribution of ZNF469 in a sample set of keratoconus patients. METHODS: Forty-three patients with keratoconus (49% Maori or Pacific [Polynesian]) were recruited. If a family history was present, family members were recruited. Participants underwent comprehensive examination, and a DNA sample was collected. Mutational analysis of ZNF469 was undertaken using Sanger sequencing, including an ancestrally matched Polynesian control population. Bioinformatic databases of exome variation and protein prediction software were used to determine presence and frequency and the pathogenicity for each observed change. RESULTS: Fourteen nonsynonymous missense single nucleotide polymorphisms (SNPs) were observed in ZNF469. Of the 43 probands, at least one probable disease-causing variant was detected in 20 (46%) (16/32 sporadic, 4/11 familial) and two variants in 5 (11.6%) (3/32 sporadic, 2/11 familial). Only heterozygous changes segregated with disease. Three "deleterious" changes observed in the Polynesian controls were removed from analysis; therefore pathogenic variants occurred in 10/43 (23.3%). CONCLUSIONS: Rare missense mutations in ZNF469, predicted to be pathogenic, occurred heterozygously, at a frequency of 23% in a keratoconus population. ZNF469 is associated with CCT in GWAS and is therefore likely to play a role in the synthesis and/or organization of corneal collagen fibers. The pathogenic changes observed either genetically predispose toward a "thin" cornea, which then becomes keratoconic, or are directly pathogenic.
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Ceratocone/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise Mutacional de DNA , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Polimorfismo de Nucleotídeo Único/genética , Adulto JovemRESUMO
BACKGROUND: The aim was to identify potential factors associated with acute corneal hydrops in a New Zealand population with keratoconus referred to a hospital eye service. METHODS: In a single hospital centre, in a retrospective review, demographic and clinical features of subjects with keratoconus and corneal hydrops over a 17-year period were compared with an age- and gender-matched control group of subjects with keratoconus but no history of corneal hydrops. RESULTS: One hundred and one eyes of 101 subjects (mean age 24.6 ± 8.4 years) were identified with keratoconus-related corneal hydrops. Subjects were more likely to be of Pacific but less likely to be of New Zealand European ethnicity than control subjects (n = 101). In comparison, Maori ethnicity was not found to have a significantly positive or negative association with hydrops. The pre-hydrops visual acuity (VA) of affected eyes was poorer than that of controls (p < 0.001) at first presentation to our tertiary referral corneal and contact lens service. Hydrops typically developed approximately four years after diagnosis of keratoconus. Subjects with hydrops were more likely to have a history of eye-rubbing (p = 0.011) but less likely to have a family history of keratoconus (p = 0.05). In 31 cases, the acute hydrops event was their first optometric/ophthalmologic contact. There were no statistically significant differences in the prevalence of atopic disease, contact lens wear or overall corneal transplantation rate between the two groups. CONCLUSIONS: Pacific ethnicity, history of eye-rubbing, poor VA at first hospital presentation and lack of family history were statistically associated with developing acute corneal hydrops in keratoconus in a New Zealand population. Greater understanding of such predisposing risk factors may help develop early management strategies to delay or prevent progression of this disease.
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Edema da Córnea/etiologia , Ceratocone/complicações , Doença Aguda , Adolescente , Adulto , Criança , Edema da Córnea/etnologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Estudos Retrospectivos , Acuidade VisualRESUMO
PURPOSE: To compare intraocular pressure (IOP) measurements after penetrating keratoplasty (PK) using Goldmann applanation tonometry (GAT; Haag-Streit USA), TonoPen XL (Reichert Inc), Pascal Dynamic Contour tonometer (PDCT; Swiss Microtechnology AG), and Ocular Response Analyzer (ORA; Reichert Inc) and to analyze effects and correlation of corneal thickness and curvature on these measurements. DESIGN: Prospective, cross-sectional study. SETTINGS: Departments of Ophthalmology, University of Auckland and Auckland District Health Board, New Zealand. STUDY POPULATION: Thirty-one eyes of 31 participants with previous PK. OBSERVATIONS: IOP measured using GAT, TonoPen, PDCT, and ORA. Central corneal thickness (CCT) and corneal astigmatism were assessed by Pentacam rotating Scheimpflug tomography. MAIN OUTCOME MEASURE: Degree of agreement in IOP measures and correlation with CCT and corneal astigmatism. RESULTS: Mean age was 44.5 ± 21.0 years and mean time since PK was 27.7 ± 28.2 months (range 3.0-122.4 months). Mean CCT was 585 ± 149 µm and mean corneal astigmatism 5.5 ± 3.8 diopters. There was no significant difference in IOP measured by GAT and TonoPen; however, both PDCT (2.12 mm Hg, P < .01) and ORA (6.29 mm Hg, P < .01) measured significantly higher IOPs compared to GAT. ORA showed the least agreement with GAT. Significant correlation was identified between each pair of measurement techniques. No instruments correlated significantly with CCT. Only PDCT showed no significant correlation with corneal astigmatism. However, no IOP measures correlated with corneal astigmatism if sutures in situ or less than 1 year post-PK. CONCLUSIONS: TonoPen or PDCT are the most suitable alternatives for measuring IOP in PK eyes where GAT readings are difficult to obtain. PDCT also offers the advantage of being independent of both CCT and corneal astigmatism.
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Pressão Intraocular/fisiologia , Ceratoplastia Penetrante , Monitorização Fisiológica , Tonometria Ocular/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Astigmatismo/fisiopatologia , Córnea/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hipertensão Ocular/prevenção & controle , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Tempo , Adulto JovemRESUMO
PURPOSE: In corneal refractive surgery, postoperative ectasia risk assessment routinely includes pachymetric analysis at the apex and thinnest point. We examined whether these data differ worldwide and constructed preliminary country-specific normative thresholds. DESIGN: This was a multicenter, cross-sectional study. METHODS: Using the Pentacam Eye Scanner (OCULUS GmbH, Wetzlar, Germany), we examined 1 randomly selected eye from each of 555 normal adults (8 countries, 6 continents), measuring the thinnest point location, central pachymetry (thinnest point, pupillary center, and apex), and the apex-thinnest point difference. International differences were assessed by 1-way analysis of variance. Normative thresholds were defined by 2- and 3-SD gates or Tukey method. RESULTS: The thinnest point averaged 0.44 mm temporal and 0.29 mm inferior to the apex. Individual thinnest points located more than 1.0 mm inferior represented fewer than 0.5% of normal corneas (>0.76 mm in the US subgroup). The mean thinnest-point pachymetry was 536 µm overall, and values less than 469 or 435 µm (-2 or -3 SD, respectively) would be expected in less than 2.5% or 0.15% of normal corneas, respectively. The thinnest-point pachymetry averaged 2 to 3 µm thinner than apical (range, 0-32 µm). Differences of greater than 8.5 µm would be expected in less than 0.5% of normal corneas overall. CONCLUSIONS: International differences were largely clinically insignificant. Nevertheless, it remains preferable to establish racial/geographic-specific normative values. We defined preliminary generalized and country-specific thresholds useful to the corneal refractive surgeon for identifying potentially abnormal corneas based on common pachymetric parameters, particularly the thinnest point by tomography.
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PURPOSE: To evaluate corneal tomographic features of keratoconus and associations between risk factors and disease phenotype in New Zealand. SETTING: Departments of Ophthalmology, University of Auckland and Auckland District Health Board, Auckland, New Zealand. DESIGN: Clinic-based, cross-sectional study. METHODS: The medical records and corneal tomography of patients attending a subspecialty service were reviewed. Data included age, sex, ethnicity, ocular history, family history, atopy, and eye rubbing. Orbscan II parameters included simulated keratometry, mean power, pachymetry, location of maximum power, anterior best-fit sphere (BFS) and posterior BFS. Morphology was categorized by the Rabinowitz topography classification. RESULTS: Final analyses included 532 eyes (266 patients; 144 men) with a mean age of 29.3 years ± 11.56 (SD). Maori and Pacific patients were overrepresented (P=.0001). Family history of keratoconus was associated with a lower mean corneal power (P=.01) and greater pachymetry (P=.03). Comparing patients with family history and patients with atopy, showed differences in thinnest-point pachymetry (mean: family history, 340 ± 15 µm; atopy 381 ± 8 µm) (P=.0218). Keratoconus was classified as severe (58.3%) or moderate (33.8%) on mean keratometry. Axial keratometric maps were predominantly asymmetric bow-tie (29%), round (18%), or inferior steepening (17%). Anterior elevation maps were classified as spur (49.3%), island (24%), irregular ridge (15%), or other (11.3%). Eighteen patients (12.5%) had complete enantiomorphism. CONCLUSIONS: Advanced keratoconus was largely asymmetric and differences in tomographic phenotype were associated with differing etiologic risk factors. Maori and Pacific ethnicities were overrepresented in this population.