Frontloading visual field tests detect earlier mean deviation progression when applied to real-world-derived early-stage glaucoma data.

PURPOSE: To examine the diagnostic accuracy of performing two (frontloaded) versus one (clinical standard) visual field (VF) test per visit for detecting the progression of early glaucoma in data derived from clinical populations. METHODS: A computer simulation model was used to follow the VFs of 10,000 glaucoma patients (derived from two cohorts: Heijl et al., Swedish cohort; and Chauhan et al., Canadian Glaucoma Study [CGS]) over a 10-year period to identify patients whose mean deviation (MD) progression was detected. Core data (baseline MD and progression rates) were extracted from two studies in clinical cohorts of glaucoma, which were modulated using SITA-Faster variability characteristics from previous work. Additional variables included follow-up intervals (six-monthly or yearly) and rates of perimetric data loss for any reason (0%, 15% and 30%). The main outcome measures were the proportions of progressors detected. RESULTS: When the Swedish cohort was reviewed six-monthly, the frontloaded strategy detected more progressors compared to the non-frontloaded method up to years 8, 9 and 10 of follow-up for 0%, 15% and 30% data loss conditions. The time required to detect 50% of cases was 1.0-1.5 years less for frontloading compared to non-frontloading. At 4 years, frontloading increased detection by 26.7%, 28.7% and 32.4% for 0%, 15% and 30% data loss conditions, respectively. Where both techniques detected progression, frontloading detected progressors earlier compared to the non-frontloaded strategy (78.5%-81.5% and by 1.0-1.3 years when reviewed six-monthly; 81%-82.9% and by 1.2-2.1 years when reviewed yearly). Accordingly, these patients had less severe MD scores (six-monthly review: 0.63-1.67 dB 'saved'; yearly review: 1.10-2.87 dB). The differences increased with higher rates of data loss. Similar tendencies were noted when applied to the CGS cohort. CONCLUSIONS: Frontloaded VFs applied to clinical distributions of MD and progression led to earlier detection of early glaucoma progression.

Quantification and Predictors of Visual Field Variability in Healthy, Glaucoma Suspect, and Glaucomatous Eyes Using SITA-Faster.

PURPOSE: The newly released Swedish Interactive Thresholding Algorithm (SITA)-Faster (SFR) has significantly shorter testing durations compared with older SITA algorithms, but its variability is uncertain. This study quantified and established threshold limits of test-retest variability across the 24-2 test grid using SFR. DESIGN: Cross-sectional study with prospective longitudinal arm. PARTICIPANTS: 1426 eyes of 787 patients with healthy, suspected glaucoma, or manifest glaucoma eyes from hospital- and university- eye clinics. METHODS: Two SFR tests per eye at a baseline visit and at two follow-up visits. MAIN OUTCOME MEASURES: Pointwise variability measured by test-retest difference in pointwise sensitivity between tests one and two, mean global variability (test-retest variance) measured by average of pointwise variability for each participant, global sensitivity, and reliability indices of each eye. RESULTS: Of the 1426 eyes, 540 eyes (37.9%) had a diagnosis of glaucoma, 753 eyes (52.8%) were suspected of having glaucoma, and the remaining 133 eyes (9.3%) were healthy. Of 74 152 pointwise sensitivities obtained, the mean test-retest difference was 2.17 ± 2.9 dB, whereas the mean test-retest variance for each participant was 2.17 ± 1.2 dB. Pointwise and global variability increased with worsening threshold sensitivity and (MD), respectively, and was greater for peripheral compared with central test locations. In the longitudinal cohort, no significant difference in mean test-retest variance was found across the 3 visits (mean variability, 2.10 dB vs. 2.16 dB vs. 2.16 dB at visits F0 vs. F1 vs. F2; P = 0.53, repeated-measures analysis of variance). Baseline MD (-0.19 dB; 95% CI, -0.22 to 0.16 dB; P < 0.0001) and abnormally high sensitivity on glaucoma hemifield test (1.14 dB; 95% CI, 0.78-1.51 dB; P < 0.0001) were significantly associated with increased variability. Finally, test-retest MD showed minimal change around the recommended 15% false-positive cutoff threshold. CONCLUSIONS: The variability of SFR increases with worsening threshold sensitivity, is stable over time, and is greater for peripheral compared with central test locations. Worse baseline MD and abnormally high sensitivity are significant predictors of increased variability. A cutoff of 15% in false-positive results may be inappropriate as a threshold for judging test reliability in SFR. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Swept-Source Anterior Segment Optical Coherence Tomography Imaging and Quantification of Bleb Parameters in Glaucoma Filtration Surgery.

This paper describes a technique for using swept-source anterior segment optical coherence tomography (AS-OCT) to visualize internal bleb microstructure and objectively quantify dimensions of the scleral flap and trabeculo-Descemet window (TDW) in non-penetrating glaucoma filtration surgery (GFS). This was a cross-sectional study of 107 filtering blebs of 67 patients who had undergone deep sclerectomy surgery at least 12 months prior. The mean post-operative follow-up duration was 6.5 years +/- 4.1 [standard deviation (SD)]. The maximal bleb height was significantly greater in the complete success (CS) blebs compared to the qualified success (QS) and failed (F) blebs (1.48 vs. 1.17 vs. 1.10 mm in CS vs. QS vs. F, one-way ANOVA, p < 0.0001). In a subcohort of deep sclerectomy blebs augmented by intraoperative Mitomycin-C, the trabeculo-Descemet window was significantly longer in the complete success compared to the qualified success group (613.7 vs. 378.1 vs. 450.8 µm in CS vs. QS vs. F, p = 0.004). The scleral flap length, thickness, and width were otherwise similar across the three outcome groups. The quantification of surgical parameters that influence aqueous outflow in non-penetrating GFS can help surgeons better understand the influence of these structures on aqueous outflow and improve surgical outcomes.

Evaluation of the Consistency of Glaucomatous Visual Field Defects Using a Clustered SITA-Faster Protocol.

PURPOSE: Frontloading SITA-Faster (SFR) visual fields (2 tests per eye on the same visit) has been shown to provide repeatable perimetric data at minimal time cost. This study reports the outcomes of using frontloaded SFR in the evaluation of pointwise visual field (VF) defects in a cohort of patients with glaucoma when transitioned from SITA-Standard (SS). DESIGN: Prospective, cross-sectional study. PARTICIPANTS: A total of 144 eyes of 91 patients with confirmed or suspected glaucoma who had an SS test on a previous visit. METHODS: Two SFR tests (T1, T2) per eye on the same visit. MAIN OUTCOME MEASURES: Global sensitivity, reliability indices, and pointwise deviation map probability scores from the pattern deviation grid of each patient were compared across the 3 sequential tests to evaluate the consistency of VF defects. RESULTS: The mean age was 68.6 years, and 79.2% of patients had a diagnosis of glaucoma. There was no significant difference in mean deviation (MD) across the 3 tests (-5.83 decibels [dB], -5.28 dB, and -5.71 dB in SS, SFR1, and SFR2, respectively, repeated-measures analysis of variance [ANOVA], P = 0.48). The frontloaded SFR tests provided repeatable VFs that confirmed existing pointwise data on the SS in 4661 (62.3%) locations, reversed an SS defect in 614 (8.2%) locations, and demonstrated a new repeatable defect in 406 (5.4%) locations of the pattern deviation grid. A new defect of at least 3 contiguous points was identified in 20.1% of eyes. The non-repeatable points on the 2 SFR tests displayed no significant difference in the distribution of defect/nondefect points based on test order or peripheral versus central locations. There was no significant difference in the rate of obtaining at least 1 reliable test result between SS and the frontloaded SFR T1 and T2 (P = 0.77). Test duration significantly decreased from SS to SFR1/2 (379 vs. 160 vs. 158 seconds, P < 0.0001). CONCLUSIONS: Frontloading SFR tests can provide repeatable data for the evaluation of the consistency of pattern deviation defects in glaucoma, with no observable decline in performance from test fatigue. This is achieved at equivalent duration and reliability as a single SS test. Frontloading SFR may be helpful in increasing testing frequency/quantity to meet recommended guidelines for progression analysis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Frontloading SITA-Faster Can Increase Frequency and Reliability of Visual Field Testing at Minimal Time Cost.

PURPOSE: To report the outcomes of frontloaded visual field (VF) testing (2 tests per eye on the same visit) over 2 longitudinal, consecutive visits using SITA-Faster (SFR) in terms of global indices, reliability metrics, and test duration. DESIGN: Prospective longitudinal study. SUBJECTS: A total of 902 eyes of 463 subjects with normal, suspect, or manifest glaucoma. METHODS: Two intravisit SFR VF tests (T1 and T2) per eye at an initial (Ti) and follow-up (Tf) visit. MAIN OUTCOME MEASURES: Intra- and intervisit global indices, reliability metrics, and test durations. RESULTS: The mean age of the subjects was 63.6 years, and 58.3% were male. Seven hundred ninety eyes (87.4%) had a diagnosis of glaucoma or glaucoma suspicion. The mean duration between visits was 265.0 (standard deviation 98.8) days. In total, 3608 VF tests were analyzed, with the correlation of mean deviation (MD) values of the frontloaded tests at each visit high (T1/T2 MD correlation at initial visit r = 0.83, root mean squared error [RMSE] = 1.26, follow-up visit r = 0.83, RMSE = 1.25, P < 0.0001) and greater than the correlation of MD between visits (Ti1/Tf1 MD correlation r = 0.72, RMSE = 1.31). There was a significant intra-visit decrease in rates of abnormally high sensitivity in the glaucoma hemifield test (3.2% vs. 1.6%, P = 0.0023) and rates of unreliable test results (15.4% vs. 9.2%, P = 0.002) from T1 to T2 in both visits, with a corresponding significant decrease in MD (-1.28 dB vs. -1.68 dB, P < 0.0001) and VF index (P = 0.03). The mean duration of each SFR test was 132.6 (SD 27.2) seconds. CONCLUSIONS: Frontloading VFs using SFR produced sets of repeatable perimetric data with significant improvement of reliability indices from the first to second test. This may help increase testing frequency at minimal time cost to meet recommended guidelines and for evaluating patients prone to high variability. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Predictors of progression in untreated keratoconus: a Save Sight Keratoconus Registry study.

AIMS: We set out to identify risk factors for progression in untreated keratoconus patients from 34 centres across Australia, New Zealand, Spain and Italy. METHODS: Patients were divided into 'progressors' and 'stable' patients for each clinical parameter: visual acuity (VA), steepest keratometry (maximum keratometry (Max-K)) and thinnest corneal thickness (TCT). Primary outcomes were the proportion of eyes with sustained progression in VA, Max-K or TCT within 3 years. Secondary outcomes included predictors of progression. RESULTS: There were 3994 untreated eyes from 2283 patients. The proportion of eyes with VA, Max-K and TCT progression at 1 year were 3.2%, 6.6% and 3.1% respectively. Factors associated with VA loss were higher baseline VA (HR 1.15 per logMAR line increase in VA; p<0.001) and steeper baseline Max-K (HR 1.07 per 1D increase; p<0.001). Younger baseline age was associated with Max-K steepening (HR 0.96 per year older; p=0.001). Thicker baseline TCT, steeper baseline Max-K and younger baseline age were associated with TCT thinning: (HR 1.08 per 10 µm increase in TCT; p<0.001), (HR 1.03 per 1D increase; p=0.02) and (HR 0.98 per year younger; p=0.01), respectively. CONCLUSIONS: Steeper Max-K and younger age were the most clinically useful baseline predictors of progression as they were associated with worsening of two clinical parameters. Every 1D steeper Max-K was associated with a 7% and 3% greater risk of worsening VA and thinning TCT, respectively. Each 1 year younger was associated with a 4% and 2% greater risk of steepening Max-K and thinning TCT, respectively.

Vision-Related Quality of Life in Keratoconus: A Save Sight Keratoconus Registry Study.

PURPOSE: To assess vision-related quality of life using the Impact of Vision Impairment Questionnaire (IVI) in patients with keratoconus enrolled in the Save Sight Keratoconus Registry. METHODS: In this cross-sectional study, data on 107 keratoconic patients were collected through a prospectively designed web-based registry from a quaternary referral eye hospital and 2 corneal subspecialty practices. Vision-related quality of life was evaluated using the IVI. Rasch analysis was used to transform the IVI responses into interval-level measures comprising reading, mobility, and emotional well-being subscales. Associations between best-corrected visual acuity (BCVA), maximum simulated keratometry (Kmax), steep keratometry (K2), and pachymetry for each eye and IVI subscale scores were evaluated with univariate (Pearson correlations) and multivariable regression adjusted for age and gender. RESULTS: Of the 107 patients, 37 (34.5%), 41 (38.0%) and 29 (26.9%) had mild, moderate, and severe keratoconus, respectively. On uni- and multivariable analysis, BCVA in the better eye had the strongest association with reading [r = 0.51; 95% confidence interval (CI), 0.35-0.64, P = 0.004] and mobility (r = 0.55; 95% CI, 0.41-0.67, P < 0.001) subscale scores. BCVA in the better and worse eye, both had the joint strongest associations with emotional scores on univariate analysis, but only the latter was significant on multivariable analysis (r = 0.37; 95% CI, 0.20-0.53, P < 0.001). K2 and Kmax in the better eye also displayed significant associations with reading and mobility scores. CONCLUSIONS: In patients with keratoconus, BCVA in the better eye had the strongest correlation with reading and mobility scores, whereas BCVA in the worse eye was significantly correlated with emotional scores.

Clinical Registries in Ophthalmology.

TOPIC: Clinical registries in ophthalmology. CLINICAL RELEVANCE: In recent years, advancements in digital technology and increasing use of electronic medical records in health systems have led to the dramatic growth in large clinical data sets. Clinical data registries are organized systems that collect data on patients diagnosed with a disease or condition or who undergo a certain procedure. METHODS: A search of the PUBMED database was conducted in January 2018 for clinical registries in ophthalmology. RESULTS: Ninety-seven clinical eye registries were found, with significant growth in numbers in the last 4 decades. The most common conditions captured were blindness or low vision, corneal transplantation, glaucoma, and cataract surgery. Most registries originate in the European region, North America, and Australia. Nine registries had multinational coverage, whereas 48 were national registries. As the numbers and scope of clinical registries have expanded, valuable observational data have been used to study real-world clinical outcomes in healthcare quality measurement and improvement and to develop new guidelines and standards. Pertinent areas of its use include studying treatments and outcomes in cataract surgery, corneal transplantation, and macular degeneration. CONCLUSIONS: The use of clinical registries for quality improvement and research has grown significantly in the last few decades, and this trend will continue as information technology infrastructures develop.

A review of scoring systems for ocular involvement in chronic cutaneous bullous diseases.

BACKGROUND: Epidermolysis bullosa (EB) and autoimmune blistering diseases (AIBD) describe a group of rare chronic dermatoses characterized by cutaneous fragility and blistering. Although uncommon, significant ocular surface disease (OSD) may occur in both and require ophthalmological assessment. Disease scoring systems have a critical role in providing objective and accurate assessment of disease severity. The objectives of this report were, firstly, to document the prevalence and severity of ocular involvement in EB/AIBD. Secondly, to review and evaluate existing ocular and systemic scoring systems for EB/AIBD. Finally, to identify areas where further development of ocular specific tools in EB/AIBD could be pursued. METHODS: A literature search was performed in October 2017 utilising Medline, Embase, and Scopus databases. The results were restricted by date of publication, between 01.01.1950 and 31.10.2017. The reference lists of these articles were then reviewed for additional relevant publications. Articles of all languages were included if an English translation was available. Articles were excluded if they were duplicates, had no reference to ocular involvement in EB/AIBD or described ocular involvement in other diseases. RESULTS: Descriptions of ocular involvement in EB/AIBD were identified in 88 peer-reviewed journal articles. Findings reported include but are not limited to: cicatrising conjunctivitis, meibomian gland dysfunction, dry eye disease, trichiasis, symblepharon, fornix fibrosis, keratopathy, ectropion/entropion, ankyloblepharon, corneal ulceration, visual impairment and blindness. Although scoring systems exist for assessment of OSD in mucous membrane pemphigoid, no such tools exist for the other AIBD subtypes or for EB. Several systemic scoring systems exist in the dermatological literature that are efficacious in grading overall EB/AIBD severity, but have limited inclusion of ocular features. To the best of our knowledge, there is no recognised or validated scoring systems which comprehensively stages or grades the spectrum of ocular manifestations in EB/AIBD. CONCLUSIONS: There are a range of ocular complications documented in EB and AIBD. Development of a comprehensive ocular scoring system for EB/AIBD which incorporates the delineation between 'activity' and 'damage' would facilitate more objective patient assessment, improved longitudinal monitoring, comparison of intervention outcomes, and provide commonality for discussion of these patients due to the multidisciplinary nature of their care.

Autoconjunctival Graft Compromise After Pterygium Surgery in a Patient Receiving Intravitreal Anti-Vascular Endothelial Growth Factor Injections.

PURPOSE: To report on a case of autoconjunctival graft compromise after pterygium surgery in a patient on long-term anti-vascular endothelial growth factor (anti-VEGF) therapy, due to the deleterious effects of anti-VEGF agents on ocular wound healing. METHODS: A white female in her early eighties presented with large right nasal pterygium, first noted 5 years previously. She also had macular degeneration and had been receiving monthly injections of ranibizumab, which was later switched to aflibercept. She proceeded to have a right nasal pterygium excision with a conjunctival autograft, 9 days after her last dose of intravitreal aflibercept. RESULTS: Surgery was uneventful; however, at the week 2 postoperative review, there was conjunctival graft dehiscence with melting of the graft and underlying sclera. The patient was administered hyperbaric oxygen treatments, topical antibiotics, steroids, and lubricating eye drops, and aflibercept injections ceased. The scleral melt slowly resolved and her aflibercept was restarted 3 months later. CONCLUSIONS: This case highlights the potential hazards of performing elective surgery in patients on VEGF inhibitors and the need for an appropriate interval between cessation/subsequent restart of anti-VEGF agents and surgery to be established.

Successful Treatment of Conjunctival Lymphangiectasia With Subconjunctival Injection of Bevacizumab.

PURPOSE: To report a novel intervention for the treatment of conjunctival lymphangiectasia-subconjunctival injection of bevacizumab. METHODS: A 53-year-old white male presented with a 3-month history of right ocular discomfort and redness unresponsive to conventional topical treatment of lubricants and steroids. A clinical diagnosis of conjunctival lymphangiectasia was confirmed by biopsy. Bevacizumab (25 mg/mL) was injected subconjunctivally into the affected area. RESULTS: An improvement in the degree of conjunctival chemosis was evident at 5 days postinjection. At 1-month follow-up, symptoms had fully resolved. No recurrence had been observed at 3 years' follow-up. CONCLUSIONS: Subconjunctival bevacizumab injection may be an effective treatment for conjunctival lymphangiectasia.

Genetic screening for human leukocyte antigen alleles prior to carbamazepine treatment.

We describe a 28-year-old Malaysian Australian man of Han Chinese descent with toxic epidermal necrolysis (TEN), occurring 2 weeks after commencing carbamazepine. He was subsequently found to be positive for human leukocyte antigen (HLA)-B*1502. Carbamazepine-induced Stevens-Johnson syndrome/TEN is strongly associated with the HLA-B*1502 allele, which is highly prevalent in Han Chinese, Malay, Thai and Indian populations. Prospective screening for the allele may prevent this cutaneous adverse drug reaction from occurring, but many neurologists and other medical practitioners are still unaware of the medico-legal risks of prescribing carbamazepine in susceptible populations and the availability of HLA-B*1502 testing. Performing HLA-B*1502 genotyping and avoiding carbamazepine in at-risk individuals has been proven to decrease incidences of drug-induced TEN. This test is widely available at most large pathology services in Australia, with results available within 2 weeks. The recommendation by regulatory bodies should be strengthened to ensure that the broad medical community is made more aware of this pertinent issue.

Prospective study of ocular manifestations of pemphigus and bullous pemphigoid identifies a high prevalence of dry eye syndrome.

PURPOSE: To study the range of ocular manifestations in an Australian cohort of patients with pemphigus and bullous pemphigoid (BP), including a detailed assessment for dry eye syndrome (DES). METHODS: Twenty-two patients with pemphigus vulgaris, pemphigus foliaceus, and BP were referred for a detailed ophthalmology review between September 2011 and March 2012. RESULTS: A total of 44 eyes of 22 patients with pemphigus vulgaris, pemphigus foliaceus, and BP were examined. Photophobia was the most common symptom reported. The most common ocular signs found in both groups were blepharitis (68.1%), conjunctival hyperemia (22.7%), and limbal broadening (18.2%). In our DES assessment, 92.9% of patients had a reduced Schirmer test score and an abnormal tear break-up time was recorded in 100% of patients. The ocular surface disease index score ranged from 0 to 47.2, with a median score of 10. CONCLUSIONS: The high occurrence of patient-reported ocular symptoms and clinical evidence of dry eye on Schirmer testing and break-up time demonstrate high prevalence of DES in our cohort of pemphigus and BP patients, which is a novel finding. Limbal broadening was another common finding not previously reported.