Novel linkage approach to join community-acquired and national data.

BACKGROUND: Community optometrists in Scotland have performed regular free-at-point-of-care eye examinations for all, for over 15 years. Eye examinations include retinal imaging but image storage is fragmented and they are not used for research. The Scottish Collaborative Optometry-Ophthalmology Network e-research project aimed to collect these images and create a repository linked to routinely collected healthcare data, supporting the development of pre-symptomatic diagnostic tools. METHODS: As the image record was usually separate from the patient record and contained minimal patient information, we developed an efficient matching algorithm using a combination of deterministic and probabilistic steps which minimised the risk of false positives, to facilitate national health record linkage. We visited two practices and assessed the data contained in their image device and Practice Management Systems. Practice activities were explored to understand the context of data collection processes. Iteratively, we tested a series of matching rules which captured a high proportion of true positive records compared to manual matches. The approach was validated by testing manual matching against automated steps in three further practices. RESULTS: A sequence of deterministic rules successfully matched 95% of records in the three test practices compared to manual matching. Adding two probabilistic rules to the algorithm successfully matched 99% of records. CONCLUSIONS: The potential value of community-acquired retinal images can be harnessed only if they are linked to centrally-held healthcare care data. Despite the lack of interoperability between systems within optometry practices and inconsistent use of unique identifiers, data linkage is possible using robust, almost entirely automated processes.

Factors associated with pathologic myopia onset and progression: A systematic review and meta-analysis.

PURPOSE: To synthesise evidence across studies on factors associated with pathologic myopia (PM) onset and progression based on the META-analysis for Pathologic Myopia (META-PM) classification framework. METHODS: Findings from six longitudinal studies (5-18 years) were narratively synthesised and meta-analysed, using odds ratio (OR) as the common measure of association. All studies adjusted for baseline myopia, age and sex at a minimum. The quality of evidence was rated using the Grades of Recommendation, Assessment, Development and Evaluation framework. RESULTS: Five out of six studies were conducted in Asia. There was inconclusive evidence of an independent effect (or lack thereof) of ethnicity and sex on PM onset/progression. The odds of PM onset increased with greater axial length (pooled OR: 2.03; 95% CI: 1.71-2.40; p < 0.001), older age (pooled OR: 1.07; 1.05-1.09; p < 0.001) and more negative spherical equivalent refraction, SER (OR: 0.77; 0.68-0.87; p < 0.001), all of which were supported by an acceptable level of evidence. Fundus tessellation was found to independently increase the odds of PM onset in a population-based study (OR: 3.02; 2.58-3.53; p < 0.001), although this was only supported by weak evidence. There was acceptable evidence that greater axial length (pooled OR: 1.23; 1.09-1.39; p < 0.001), more negative SER (pooled OR: 0.87; 0.83-0.92; p < 0.001) and higher education level (pooled OR: 3.17; 1.36-7.35; p < 0.01) increased the odds of PM progression. Other baseline factors found to be associated with PM progression but currently supported by weak evidence included age (pooled OR: 1.01), severity of myopic maculopathy (OR: 3.61), intraocular pressure (OR: 1.62) and hypertension (OR: 0.21). CONCLUSIONS: Most PM risk/prognostic factors are not supported by an adequate evidence base at present (an indication that PM remains understudied). Current factors for which an acceptable level of evidence exists (limited in number) are unmodifiable in adults and lack personalised information. More longitudinal studies focusing on uncovering modifiable factors and imaging biomarkers are warranted.

Measuring axial length of the eye from magnetic resonance brain imaging.

BACKGROUND: Metrics derived from the human eye are increasingly used as biomarkers and endpoints in studies of cardiovascular, cerebrovascular and neurological disease. In this context, it is important to account for potential confounding that can arise from differences in ocular dimensions between individuals, for example, differences in globe size. METHODS: We measured axial length, a geometric parameter describing eye size from T2-weighted brain MRI scans using three different image analysis software packages (Mango, ITK and Carestream) and compared results to biometry measurements from a specialized ophthalmic instrument (IOLMaster 500) as the reference standard. RESULTS: Ninety-three healthy research participants of mean age 51.0 ± SD 5.4 years were analyzed. The level of agreement between the MRI-derived measurements and the reference standard was described by mean differences as follows, Mango - 0.8 mm; ITK - 0.5 mm; and Carestream - 0.1 mm (upper/lower 95% limits of agreement across the three tools ranged from 0.9 mm to - 2.6 mm). Inter-rater reproducibility was between - 0.03 mm and 0.45 mm (ICC 0.65 to 0.93). Intra-rater repeatability was between 0.0 mm and - 0.2 mm (ICC 0.90 to 0.95). CONCLUSIONS: We demonstrate that axial measurements of the eye derived from brain MRI are within 3.5% of the reference standard globe length of 24.1 mm. However, the limits of agreement could be considered clinically significant. Axial length of the eye obtained from MRI is not a replacement for the precision of biometry, but in the absence of biometry it could provide sufficient accuracy to act as a proxy. We recommend measuring eye axial length from MRI in studies that do not have biometry but use retinal imaging to study neurodegenerative changes so as to control for differing eye size across individuals.

Paediatric glaucoma in Scotland.

BACKGROUND: The primary aim was to estimate the incidence of primary and secondary childhood glaucoma in Scotland over a 2-year period. The secondary aim was to gauge the confidence and experience of ophthalmologists in Scotland in managing these patients. METHODS: A 7 question electronic survey was distributed to all consultant members of the Scottish Paediatric Club and Scottish Glaucoma Club. Respondents were asked to report the number of cases and types of childhood glaucoma they had managed in the last 2 years. Respondents were also asked about experience and confidence in a range of glaucoma procedures, number of patients requiring referral to specialist centres and interest in the development of a centre of excellence in Scotland. RESULTS: The survey returned a 56% response rate, reporting 85 new cases of paediatric glaucoma in Scotland over the preceding 2 years. 11 (12.9%) had primary glaucoma and 74 (87.1%) had secondary glaucoma. The most common subtype of secondary glaucoma was uveitic glaucoma (n = 29). None of the respondents declared confidence or experience in trabeculotomy or goniotomy procedures. Eleven children required referral to a specialist unit outside Scotland. 85.7% of respondents felt Scotland would benefit from a specialist unit for paediatric glaucoma. CONCLUSIONS: This survey reflects an appetite for a specialist service for paediatric glaucoma in Scotland. However, further consideration is needed to determine if there is sufficient patient load to maintain such a service.

Speed and accuracy of saccades in patients with glaucoma evaluated using an eye tracking perimeter.

BACKGROUND: To examine the speed and accuracy of saccadic eye movements during a novel eye tracking threshold visual field assessment and determine whether eye movement parameters may improve ability to detect glaucoma. METHODS: A prospective study including both eyes of 31 patients with glaucoma and 23 controls. Standard automated perimetry (SAP) and eye tracking perimetry (saccadic vector optokinetic perimetry, SVOP) was performed. SVOP provided data on threshold sensitivity, saccade latency, and two measures of accuracy of saccades (direction bias and amplitude bias). The relationship between eye movement parameters and severity of glaucoma was examined and Receiver Operating Characteristic curves were used to assess ability to detect glaucoma. RESULTS: Patients with glaucoma had significantly slower saccades (602.9 ± 50.0 ms versus 578.3 ± 44.6 ms for controls, P = 0.009) and reduced saccade accuracy (direction bias = 7.4 ± 1.8 versus 6.5 ± 1.5 degrees, P = 0.006). There was a significant slowing of saccades and saccades became less accurate with worsening SAP sensitivity. Slower saccades were associated with increased odds of glaucoma; however, the AUC for saccade latency was only 0.635 compared to 0.914 for SVOP sensitivity. CONCLUSION: Patients with glaucoma had significant differences in eye movements compared to healthy subjects, with a relationship between slower and less accurate eye movements and worse glaucoma severity. However, in a multivariable model, eye movement parameters were not of additional benefit in differentiating eyes with glaucoma from healthy controls.

The role of the disc damage likelihood scale in glaucoma detection by community optometrists.

PURPOSE: Recent guidelines recommend disc damage likelihood scale (DDLS) is recorded for all referrals of suspected glaucoma from community optometrists to hospital eye services (HES) in Scotland. This study aimed to determine whether lower DDLS grades were associated with higher rates of discharge at the first visit to HES. METHODS: A retrospective analysis of 618 consecutive new referrals from community optometrists to a university hospital glaucoma service. 65 (10.5%) included DDLS graded by the community optometrist. A comprehensive eye examination and optical coherence tomography (OCT) was performed in the hospital glaucoma clinic and first visit discharge rate (FVDR) for different grades of DDLS compared. The relationship between DDLS and retinal nerve fibre layer (RNFL) thickness on OCT was also examined. RESULTS: The FVDR for patients with DDLS recorded in the referral was 27.7% (18 of 65) compared to 25% (138 of 553) in those without DDLS (p = 0.631). The FVDR was 50% for those with a DDLS of 3 in the worse eye, decreasing to 32% and 21% for DDLS grades of 4 and 5 respectively. No patient with a DDLS ≥ 6 was discharged at the first visit and none with a DDLS < 4 (the cut off for consideration of referral in Scottish guidelines) were found to have glaucoma. There was a significant but weak inverse relationship between DDLS and RNFL thickness. The strongest relationship was with average RNFL thickness (r = -0.378, p < 0.01) followed by superotemporal (r = -0.359, p < 0.01) and inferotemporal (r = -0.353, p < 0.01) RNFL thickness. CONCLUSIONS: In patients referred to HES with DDLS information included, lower DDLS grading was associated with higher odds of being discharged at the first visit. DDLS grading by community optometrists had a poor correlation with RNFL thickness measured using OCT.

Accuracy of detection of patients with narrow angles by community optometrists in Scotland.

AIM: To examine the accuracy of referrals by community optometrists for suspected primary angle closure, including primary angle closure suspects, primary angle closure and primary angle closure glaucoma. METHODS: A retrospective review of 769 consecutive patients referred by community optometrists to the glaucoma clinic at a university hospital in Scotland. Ninety-five of 715 eligible subjects (13%) were referred due to suspected angle closure. All subjects had a comprehensive eye examination in the glaucoma clinic, including gonioscopy, with angle closure defined according to the International Society of Geographical and Epidemiological Ophthalmology classification as iridotrabecular contact over at least 270 degrees. RESULTS: Fifty-nine of 95 subjects referred due to suspected angle closure were confirmed to have an occludable angle, while 36 of 95 (38%) had open angles (positive predictive value = 62%). Of 620 patients referred to the glaucoma clinic for reasons other than narrow angles, 601 (97%) had open angles on gonioscopy and 19 (3%) had narrow angles. Using the 620 patients referred with 'open angles' as a control group, sensitivity was estimated as 76% and specificity 94%. Eleven of 95 (12%) patients referred for possible angle closure were discharged at the first visit compared to 156 of 620 (25%) referred to the glaucoma clinic for other reasons (p = 0.003). In a multivariable model, suspect angle closure detected by the optometrist (OR = 56.0, 95% CI 35.2-89.2, p < 0.001) and female gender (OR = 1.9, 95% CI 1.2-3.1, p = 0.008) were associated with increased odds of angle closure on gonioscopy. CONCLUSION: Community optometrists had good ability to detect eyes at risk of angle closure. There was also greater accuracy of referrals for suspected angle closure than for other glaucoma referrals.

Event-based analysis of visual field change can miss fast glaucoma progression detected by a combined structure and function index.

PURPOSE: To investigate the relationship between progression assessed by the visual field guided progression analysis (GPA) and rates of structural and functional change in glaucoma eyes. METHODS: This was a longitudinal observational study of 135 eyes of 97 patients with glaucoma followed for an average of 3.5 ± 0.9 years. All patients had standard automated perimetry (SAP) and retinal nerve fiber layer (RNFL) analysis with spectral domain optical coherence tomography (SDOCT), with an average of 6.8 ± 2.3 visits. A control group of healthy eyes followed longitudinally was used to estimate age-related change. Visual field progression was assessed using the Humphrey Field Analyzer GPA. Estimates of retinal ganglion cell counts from SAP and SDOCT were used to obtain a combined index of glaucomatous damage (RGC index) according to a previously described algorithm. Progression by SDOCT and the retinal ganglion cell (RGC) index were defined as statistically significant (P < 0.05) slopes of change that were also faster than age-related change estimated from healthy eyes. RESULTS: From the 135 eyes, 15 (11%) progressed by GPA, 21 (16%) progressed by SDOCT, and 31 (23%) progressed by the RGC index. Twenty-one eyes showed progression by the RGC index that was missed by the GPA. These eyes had an average rate of change in estimated RGC counts of - 28,910 cells/year, ranging from two to nine times faster than expected age-related losses. CONCLUSION: Many glaucomatous eyes that are not found to be progressing by GPA may actually have fast rates of change as detected by a combined index of structure and function.

Glaucoma management in primary care: barriers perceived by optometrists in Scotland.

PURPOSE: Over the next 10 years, the prevalence of glaucoma in the United Kingdom (UK) is predicted to rise by 22%,(The Way Forward: Glaucoma, The Royal College of Ophthalmologists, London, 2017) posing a considerable challenge to already overstretched hospital eye services. To help address this problem, services traditionally offered in hospital such as managing stable glaucoma patients, could be transferred to community optometrists. The aim of this study was to identify whether optometrists in Scotland have an interest in managing primary open angle glaucoma (POAG) in primary care and to assess perceived barriers. METHODS: All optometrists on the NHS Education Scotland (NES) database were invited to participate in an online survey over a 7-week period. Optometrists were asked if they had an interest in being accredited to manage POAG in the community and a free text question was used to elicit perceived barriers. Responders with an interest in managing POAG were invited to take part in two further rounds of electronic surveying, using a modified Delphi approach, with the aim of reaching a consensus on perceived barriers. RESULTS: Two hundred and ninety-nine of 1566 optometrists (19%) responded to the survey. 229 (79%) expressed an interest in managing patients with POAG in primary care. The most commonly perceived barriers after two rounds of Delphi surveying were remuneration (29%), communication with secondary care (18%), perceived ophthalmology resistance (13%), training (11%) and capacity (10%). Multivariate regression revealed fewer years in practice and comfort using and interpreting results of pachymetry were associated with higher odds of interest in managing glaucoma in the community. CONCLUSIONS: Among survey responders, there was significant interest from community optometrists to being accredited to manage POAG in primary care. A collaborative approach between primary and secondary care will be required to address the concerns of community optometrists in any future expansion of their role in glaucoma management.

Detecting Structural Progression in Glaucoma with Optical Coherence Tomography.

Optical coherence tomography (OCT) is increasingly used to obtain objective measurements of the retinal nerve fiber layer (RNFL), optic nerve head, and macula for assessing glaucoma progression. Although OCT has been adopted widely in clinical practice, uncertainty remains concerning its optimal role. Questions include: What is the best structure to measure? What quantity of change is significant? Are structural changes relevant to the patient? How are longitudinal measurements affected by aging? How can changes resulting from aging be differentiated from true progression? How best should OCT be used alongside visual fields, and how often should OCT be performed? Recent studies have addressed some of these questions. Important developments include appreciation of the need to use a consistent point of reference for structural measurements, leading to the introduction of Bruch's membrane opening (BMO)-based measurements, including BMO-minimum rim width and BMO-minimum rim area. Commercially available OCT devices also permit analysis of macular changes over time, for example, changes in the ganglion cell and inner plexiform layers, the sites of the retinal ganglion cell bodies and dendrites, respectively. Several longitudinal studies have compared rates of change in RNFL and macular measurements, with some suggesting that the relative value of each parameter may differ at different stages of disease. In early disease, looking for change over time also may be useful for glaucoma diagnosis, with advantages over classifying eyes using cross-sectional normative databases. Optimal glaucoma management requires information from imaging and visual fields, and efforts have been made to combine information, reducing the noise inherent in both tests to benefit from their different performances according to the stage of disease. Combining information from different structural measurements may also be useful. There is now substantial evidence that progressive structural changes are of direct clinical relevance, with progressive changes on OCT often preceding functional loss and patients with faster change on OCT at increased risk of worsening visual losses. Identification of such patients offers the possibility of commencing or escalating treatment at an earlier stage. This review appraises recent developments in the use of OCT for assessing glaucoma progression.

A national survey of the use of pachymeters by optometrists in Scotland: experience, views and barriers to use.

PURPOSE: Thin central corneal thickness (CCT) is a risk factor for glaucoma. In 2016 all optometry practices in Scotland were provided with pachymeters aiming to improve risk assessment and accuracy of referrals to secondary care. We examined optometrists' experience and views of pachymetry, including perceived barriers to pachymetry in primary care. METHODS: A questionnaire was sent using the REDCap electronic data capture tool to all 1264 optometrists registered with NHS Education for Scotland (NES). The questionnaire evaluated year of qualification, previous pachymetry training, confidence performing and interpreting pachymetry, and perceived indications for and barriers to use. RESULTS: Respondents numbered 418 out of 1264 (33%) optometrists, of whom 56% had previous training in pachymetry. Those that had previous training were significantly more likely to report pachymetry to be useful, with median (inter-quartile range) usefulness score of 86 (71-98) where 0 indicated not at all useful, and 100 extremely useful, vs 76 (58-90), Wilcoxon-Mann-Whitney test, z = -4.67, p < 0.01. There are no valid scales for adjusting intraocular pressure (IOP) using CCT, however 45% of respondents reported using a scale. Optometrists planned to use pachymetry when assessing patients with ocular hypertension or suspected glaucoma. The greatest perceived barrier was the process of decontaminating or cleaning the pachymeter between patients, followed by lack of time and lack of training. CONCLUSIONS: Although the majority of optometrists were interested in performing pachymetry, many lacked confidence in performing and interpreting the results. Forty-one percent of those who reported training in pachymetry still used non-validated scales to convert IOP measurements illustrating the need for further training.

24-Hour Contact Lens Sensor Monitoring of Intraocular Pressure-Related Profiles in Normal-Tension Glaucoma and Rates of Disease Progression.

PURPOSE: To determine the relationship between the rate of glaucomatous visual field loss and the amplitude of a 24-h intraocular pressure (IOP)-related profile measured using a contact lens sensor (CLS). METHODS: This observational study included 22 patients with glaucoma and an IOP of consistently ≤21 mm Hg during office hours. All subjects underwent Goldmann tonometry, standard automated perimetry (SAP), dilated fundus examination, and had a CLS recording. A cosine function was used to obtain peak (acrophase), trough (bathyphase), and amplitude measurements. Prior rates of change in SAP mean deviation were calculated and compared to CLS parameters. RESULTS: The patients had a mean (± SD) age of 66.6 ± 8.2 years (range 54-89 years). Mean follow-up was 6.6 ± 5.0 years with 8.3 ± 3.2 reliable SAP tests. The mean rate of change in SAP was -0.86 ± 1.0 dB per year (range -0.11 to -2.12 dB). Regression analysis suggested faster rates of prior visual field loss in eyes with higher-amplitude CLS curves, but this did not reach statistical significance (R2 = 0.174, p = 0.053). The CLS accurately identified waking and sleeping periods. 59.1% of eyes had a nocturnal acrophase (peaking between 23:00 and 07:00). There was no significant difference in rates of visual field change between patients with nocturnal or diurnal acrophase (-0.71 ± 1.17 and -1.07 ± 0.84 dB/year, respectively, p = 0.437). CONCLUSION: CLS recordings in patients with normal-tension glaucoma (defined by office hours IOP) indicated that 60% of patients had peak IOP during nocturnal hours, which may not be captured using conventional methods of IOP measurement. Novel parameters obtained using the CLS may provide information for predicting the risk of visual field changes for patients with glaucoma.

Rate and Pattern of Rim Area Loss in Healthy and Progressing Glaucoma Eyes.

PURPOSE: To characterize the rate and pattern of age-related and glaucomatous neuroretinal rim area changes in subjects of African and European descent. DESIGN: Prospective longitudinal study. PARTICIPANTS: Two hundred ninety-six eyes of 157 healthy subjects (88 patients of African descent and 69 of European descent) and 73 progressing glaucoma eyes of 67 subjects (24 patients of African descent and 43 of European descent) from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study were included. METHODS: Global and sectoral rim areas were measured using confocal laser scanning ophthalmoscopy. Masked stereophotograph review determined progression of glaucomatous optic disc damage. The rates of absolute rim area loss and percentage rim area loss in healthy and progressing glaucomatous eyes were compared using multivariate, nested, mixed-effects models. MAIN OUTCOME MEASURES: Rate of rim area loss over time. RESULTS: The median follow-up time was 5.0 years (interquartile range, 2.0-7.4 years) for healthy eyes and 8.3 years (interquartile range, 7.5-9.9 years) for progressing glaucoma eyes. The mean rate of global rim area loss was significantly faster in progressing glaucomatous eyes compared with healthy eyes for both rim area loss (-10.2×10(-3) vs. -2.8×10(-3) mm(2)/year, respectively; P < 0.001) and percentage rim area loss (-1.1% vs. -0.2%/year, respectively; P < 0.001), but considerable overlap existed between the 2 groups. Sixty-three percent of progressing glaucoma eyes had a rate of change faster than the fifth quantile of healthy eyes. For both healthy and progressing eyes, the pattern of rim area loss and percentage rim area loss were similar, tending to be fastest in the superior temporal and inferior temporal sectors. The rate of change was similar in progressing eyes of patients of African or European descent. CONCLUSIONS: Compared with healthy eyes, the mean rate of global rim area loss was 3.7 times faster and the mean rate of global percentage rim area loss was 5.4 times faster in progressing glaucoma eyes. A reference database of healthy eyes can be used to help clinicians distinguish age-related rim area loss from rim area loss resulting from glaucoma.

Rates of Retinal Nerve Fiber Layer Loss in Contralateral Eyes of Glaucoma Patients with Unilateral Progression by Conventional Methods.

PURPOSE: To determine whether progressive retinal nerve fiber layer (RNFL) loss occurs in the contralateral eye of patients with glaucoma showing unilateral progression according to conventional diagnostic methods. DESIGN: Prospective, longitudinal, observational cohort study. PARTICIPANTS: Three hundred forty-six eyes of 173 patients (118 eyes with glaucoma and 228 eyes with suspect glaucoma at baseline) followed up for an average of 3.5±0.7 years. METHODS: All subjects underwent standard automated perimetry (SAP; Humphrey Field Analyzer; Carl Zeiss Meditec, Dublin, CA) and spectral-domain (SD) optical coherence tomography (OCT; Spectralis; Heidelberg Engineering, Inc., Carlsbad, CA) in both eyes at 6-month intervals. Eyes were determined as progressing by conventional methods if there was progression on masked grading of optic disc stereophotographs or SAP Guided Progression Analysis (GPA; Carl Zeiss Meditec; "likely progression"). Rates of change in SD OCT average RNFL thickness were obtained using a linear mixed effects model. Rate of global loss was calculated using a random coefficient model and compared for nonprogressing patients, progressing eyes, and fellow eyes of unilateral progressing patients. MAIN OUTCOMES MEASURES: Rate of change in global RNFL thickness. RESULTS: Thirty-nine subjects showed evidence of unilateral progression by GPA, disc photographs, or both during follow-up. Mean ± standard error rate of RNFL loss in eyes progressing by conventional methods was -0.89±0.22 µm/year (P<0.001). The contralateral eyes of these subjects also showed significant loss of RNFL over time (-1.00±0.20 µm/year; P<0.001). One hundred thirty-four subjects did not show progression by conventional methods in either eye. These eyes also showed a significant decline over time in average RNFL thickness (-0.71±0.09 µm/year; P<0.001); however, the rate of change in these eyes was slower than that of the contralateral eye of patients showing unilateral progression (P<0.001). CONCLUSIONS: Loss of RNFL thickness was seen in a substantial number of contralateral eyes of glaucoma patients showing unilateral progression by conventional methods. These findings indicate that assessment of RNFL thickness by SD OCT may show progressive glaucomatous damage that is not detected by visual fields or optic disc stereophotography.

Defects of the lamina cribrosa in eyes with localized retinal nerve fiber layer loss.

OBJECTIVE: To determine whether focal abnormalities of the lamina cribrosa (LC) are present in glaucomatous eyes with localized retinal nerve fiber layer (RNFL) defects. DESIGN: Cross-sectional, observational study. PARTICIPANTS: We analyzed 20 eyes of 14 subjects with localized RNFL defects detected by masked grading of stereophotographs and 40 eyes of 25 age-matched healthy subjects recruited from the Diagnostic Innovations in Glaucoma Study at the University of California, San Diego. METHODS: All eyes had stereoscopic optic disc photography and in vivo LC imaging using enhanced depth imaging optical coherence tomography (EDI-OCT). Two masked graders identified focal LC defects defined by a standardized protocol using 48 radial scan EDI-OCT images. The kappa coefficient was calculated as a measure of the reliability of interobserver agreement. MAIN OUTCOME MEASURES: The number of focal LC defects and the relationship between the location of LC defects and the location of localized RNFL defects. RESULTS: Of 20 eyes with a localized RNFL defect, 15 (75%) had ≥1 LC defect compared with only 1 of 40 healthy eyes (3%). There were 13 eyes with localized RNFL defects that had 1 LC defect, 1 eye with 2 LC defects, and 1eye with 3 LC defects. The largest area LC defect was present in a radial line EDI-OCT scan corresponding with a localized RNFL defect in 13 of 15 eyes (87%). There was good agreement between graders as to whether an eye had an LC defect (kappa = 0.87; 95% confidence interval [CI], 0.73-1.00; P<0.001) and the location of the largest defect (kappa = 0.72; 95% CI, 0.44-1.00; P<0.001). CONCLUSIONS: Focal defects of the LC were frequently visible in glaucomatous eyes with localized RNFL defects. Focal abnormalities of the LC may be associated with focal retinal nerve fiber damage.

Detecting glaucoma using automated pupillography.

OBJECTIVE: To evaluate the ability of a binocular automated pupillograph to discriminate healthy subjects from those with glaucoma. DESIGN: Cross-sectional observational study. PARTICIPANTS: Both eyes of 116 subjects, including 66 patients with glaucoma in at least 1 eye and 50 healthy subjects from the Diagnostic Innovations in Glaucoma Study. Eyes were classified as glaucomatous by repeatable abnormal standard automated perimetry (SAP) or progressive glaucomatous changes on stereophotographs. METHODS: All subjects underwent automated pupillography using the RAPDx pupillograph (Konan Medical USA, Inc., Irvine, CA). MAIN OUTCOME MEASURES: Receiver operating characteristic (ROC) curves were constructed to assess the diagnostic ability of pupil response parameters to white, red, green, yellow, and blue full-field and regional stimuli. A ROC regression model was used to investigate the influence of disease severity and asymmetry on diagnostic ability. RESULTS: The largest area under the ROC curve (AUC) for any single parameter was 0.75. Disease asymmetry (P <0.001), but not disease severity (P = 0.058), had a significant effect on diagnostic ability. At the sample mean age (60.9 years), AUCs for arbitrary values of intereye difference in SAP mean deviation (MD) of 0, 5, 10, and 15 dB were 0.58, 0.71, 0.82, and 0.90, respectively. The mean intereye difference in MD was 2.2±3.1 dB. The best combination of parameters had an AUC of 0.85; however, the cross-validated bias-corrected AUC for these parameters was only 0.74. CONCLUSIONS: Although the pupillograph had a good ability to detect glaucoma in the presence of asymmetric disease, it performed poorly in those with symmetric disease.

Use of statistical analyses in the ophthalmic literature.

PURPOSE: To identify the most commonly used statistical analyses in the ophthalmic literature and to determine the likely gain in comprehension of the literature that readers could expect if they were to add knowledge of more advanced techniques sequentially to their statistical repertoire. DESIGN: Cross-sectional study. METHODS: All articles published from January 2012 through December 2012 in Ophthalmology, the American Journal of Ophthalmology, and Archives of Ophthalmology were reviewed. A total of 780 peer-reviewed articles were included. Two reviewers examined each article and assigned categories to each one depending on the type of statistical analyses used. Discrepancies between reviewers were resolved by consensus. MAIN OUTCOME MEASURES: Total number and percentage of articles containing each category of statistical analysis were obtained. Additionally, we estimated the accumulated number and percentage of articles that a reader would be expected to be able to interpret depending on their statistical repertoire. RESULTS: Readers with little or no statistical knowledge would be expected to be able to interpret the statistical methods presented in only 20.8% of articles. To understand more than half (51.4%) of the articles published, readers would be expected to be familiar with at least 15 different statistical methods. Knowledge of 21 categories of statistical methods was necessary to comprehend 70.9% of articles, whereas knowledge of more than 29 categories was necessary to comprehend more than 90% of articles. Articles related to retina and glaucoma subspecialties showed a tendency for using more complex analysis when compared with articles from the cornea subspecialty. CONCLUSIONS: Readers of clinical journals in ophthalmology need to have substantial knowledge of statistical methodology to understand the results of studies published in the literature. The frequency of the use of complex statistical analyses also indicates that those involved in the editorial peer-review process must have sound statistical knowledge to appraise critically the articles submitted for publication. The results of this study could provide guidance to direct the statistical learning of clinical ophthalmologists, researchers, and educators involved in the design of courses for residents and medical students.

Relationship between ganglion cell layer thickness and estimated retinal ganglion cell counts in the glaucomatous macula.

PURPOSE: To investigate the relationship between macular ganglion cell-inner plexiform layer (mGCIPL) thickness and estimated macular retinal ganglion cell (RGC) counts in glaucoma. DESIGN: Observational cohort study. PARTICIPANTS: Cross-sectional study of 77 healthy, 154 glaucoma suspect, and 159 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study. METHODS: All eyes underwent 24-2 standard automated perimetry (SAP) and optic nerve and macular imaging using high-definition optical coherence tomography (OCT). The total number of RGCs was estimated using a previously described model that uses SAP and OCT circumpapillary retinal nerve fiber layer (cpRNFL) measurements. The number of macular RGCs was estimated from the temporal cpRNFL and SAP test points within the central 10°. MAIN OUTCOME MEASURES: The correlation between mGCIPL thickness and estimates of macular RGC counts. RESULTS: The average estimated macular RGC count in glaucomatous eyes was 306 010 ± 109 449 cells, which was significantly lower than the estimate of 520 678 ± 106 843 cells in healthy eyes (P < 0.001). Glaucomatous eyes had 41% fewer estimated macular RGCs than healthy eyes and suspects had 21% fewer estimated macular RGCs. There was strong correlation between estimated macular RGC counts and mGCIPL thickness (R(2) = 0.67; P < 0.001). Macular RGC counts performed better than average mGCIPL thickness in discriminating healthy and glaucomatous eyes with receiver operating characteristic curve areas of 0.873 and 0.775, respectively (P = 0.015). CONCLUSIONS: The strong association between estimated macular RGC counts and mGCIPL thickness and the better diagnostic performance of the macular RGC counts compared with mGCIPL thickness provides further evidence that estimates of RGC number from cpRNFL thickness and SAP sensitivity can be used to assess neural losses in glaucoma.

Predicting progression of glaucoma from rates of frequency doubling technology perimetry change.

PURPOSE: To evaluate the ability of longitudinal frequency doubling technology (FDT) to predict the development of glaucomatous visual field loss on standard automated perimetry (SAP) in glaucoma suspects. DESIGN: Prospective, observational cohort study. PARTICIPANTS: The study included 587 eyes of 367 patients with suspected glaucoma at baseline selected from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES). These eyes had an average of 6.7 ± 1.9 FDT tests during a mean follow-up time of 73.1 ± 28.0 months. METHODS: Glaucoma suspects had intraocular pressure (IOP) >21 mmHg or an optic disc appearance suspicious of glaucoma. All patients had normal or nonrepeatable abnormal SAP at baseline. Humphrey Matrix FDT (Carl Zeiss Meditec, Inc, Dublin, CA) testing was performed within 6 months of SAP testing. The study end point was the development of 3 consecutive abnormal SAP test results. Joint longitudinal survival models were used to evaluate the ability of rates of FDT pattern standard deviation (PSD) change to predict the development of visual field loss on SAP, adjusting for confounding variables (baseline age, mean IOP, corneal thickness, and follow-up measurements of SAP PSD). MAIN OUTCOME MEASURES: The R(2) index was used to evaluate and compare the predictive abilities of the model containing longitudinal FDT PSD data with the model containing only baseline data. RESULTS: Sixty-three of 587 eyes (11%) developed SAP visual field loss during follow-up. The mean rate of FDT PSD change in eyes that developed SAP visual field loss was 0.07 dB/year versus 0.02 dB/year in those that did not (P < 0.001). Baseline FDT PSD and slopes of FDT PSD change were significantly predictive of progression, with hazard ratios of 1.11 per 0.1 dB higher (95% confidence interval [CI], 1.04-1.18; P = 0.002) and 4.40 per 0.1 dB/year faster (95% CI, 1.08-17.96; P = 0.04), respectively. The longitudinal model performed significantly better than the baseline model with an R(2) of 82% (95% CI, 74-89) versus 11% (95% CI, 2-24), respectively. CONCLUSIONS: Rates of FDT PSD change were highly predictive of the development of SAP visual field loss in glaucoma suspects. This finding suggests that longitudinal FDT evaluation may be useful for risk stratification of patients with suspected glaucoma.

Visual improvement following glaucoma surgery: a case report.

BACKGROUND: Glaucoma is a progressive optic neuropathy and a leading cause of blindness. Neural losses from glaucoma are irreversible, and so the aim of glaucoma treatment is to slow progression and minimize the risk of further damage. Functional improvement with treatment is not expected. We report the case of a patient who experienced a significant improvement in vision following glaucoma surgery and review the literature regarding this phenomenon. CASE PRESENTATION: A 64-year old male presented with a 13-month history of gradual vision loss in the right eye to the extent that he could only perceive hand movements. His intraocular pressure (IOP) measured 50 mmHg and he was found to have advanced primary open angle glaucoma. Medical treatment was commenced and he underwent a successful right Mitomycin C-augmented trabeculectomy. Unexpectedly he experienced marked improvement in vision post-operatively, with improvements maintained through six months of follow-up. At his most recent visit visual acuity was 6/18 in the affected eye. Although the mechanism of improved vision cannot be proven it is likely that successful lowering of IOP resulted in some reversal of retinal ganglion cell dysfunction. Important factors may have included his relatively young age, high IOP and short duration of symptoms. CONCLUSION: Although rare, functional improvements may occur following trabeculectomy. Glaucoma surgery should be offered early to those with advanced disease, and considered even in those with reduced visual acuity.