Fast Progressors in Glaucoma: Prevalence Based on Global and Central Visual Field Loss.

PURPOSE: To determine the prevalence of fast global and central visual field (VF) progression in individuals with glaucoma under routine care. DESIGN: Observational study. PARTICIPANTS: Six hundred ninety-three eyes of 461 individuals with glaucoma followed up over a median of 4.5 years. METHODS: This study included (1) patients at a private ophthalmology clinic in Melbourne, Australia, and (2) individuals in 2 prospective longitudinal observational studies across 3 sites in the United States. All individuals had a diagnosis of glaucoma and were under routine care, and had performed 5 or more reliable 24-2 VF tests over a 1- to 5-year period. Ordinary least squares regression analyses were used to calculate the rate of global mean deviation (MD) change over time and the rate of the mean total deviation values of the 12 test locations within the central 10° region (MTD10) for each eye. MAIN OUTCOME MEASURES: Prevalence of progression based on the rate of MD and the MTD10 change across various fixed cutoffs and cutoffs based on the estimated normal distribution (from the positive slopes). RESULTS: Based on the MD and the MTD10, 12.5% and 11.7% of the eyes, respectively, exhibited a rate of change that was less than -1.0 dB/year (being a rate that typically is defined as "fast progression" for MD values), and 29.0% of the eyes showed a change of less than -0.5 dB/year on MTD10. Furthermore, 12.7% and 9.1% of the eyes exhibited a rate of change that exceeded the 1% cutoff of the estimated normal distribution MD and the MTD10 values, respectively. CONCLUSIONS: This study found that approximately 1 in 8 eyes with glaucoma receiving routine care showed fast progression based on global MD values (< -1.0 dB/year) and that nearly 1 in 3 eyes showed a < -0.5 dB/year decline centrally. These findings highlight the clinical importance of assessing progressive central VF loss and reinforce the need for new therapies to prevent functional disability in a notable proportion of individuals who continue to exhibit fast progression. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

The genetic and clinical landscape of nanophthalmos and posterior microphthalmos in an Australian cohort.

Nanophthalmos and posterior microphthalmos are ocular abnormalities in which both eyes are abnormally small, and typically associated with extreme hyperopia. We recruited 40 individuals from 13 kindreds with nanophthalmos or posterior microphthalmos, with 12 probands subjected to exome sequencing. Nine probands (69.2%) were assigned a genetic diagnosis, with variants in MYRF, TMEM98, MFRP, and PRSS56. Two of four PRSS56 families harbored the previously described c.1066dupC variant implicated in over half of all reported PRSS56 kindreds, with different surrounding haplotypes in each family suggesting a mutational hotspot. Individuals with a genetic diagnosis had shorter mean axial lengths and higher hyperopia than those without, with recessive forms associated with the most extreme phenotypes. These findings detail the genetic architecture of nanophthalmos and posterior microphthalmos in a cohort of predominantly European ancestry, their relative clinical phenotypes, and highlight the shared genetic architecture of rare and common disorders of refractive error.

Effect of phacoemulsification on trabeculectomy function.

BACKGROUND: To evaluate the effect of phacoemulsification on trabeculectomy function. DESIGN: Retrospective case-control study. PARTICIPANTS: Forty-eight patients who underwent trabeculectomy surgery and had at least 2 years of follow up. METHODS: Patients were classified into two groups: patients who had phacoemulsification subsequent to trabeculectomy (Trab_phaco, n = 18) and patients who were pseudophakic for greater than 6 months preceding their trabeculectomy (Phaco_trab, n = 30). Groups were matched for length of follow up of 2 years from time of trabeculectomy. MAIN OUTCOME MEASURES: The primary outcome measures were target intraocular pressure of criteria A, ≤12 mmHg; B, ≤15 mmHg; C, ≤18 mmHg with or without additional topical treatment. A separate measure for bleb function failure was also used; with failure defined as the need for additional topical antiglaucoma therapy or surgical intervention to achieve control of intraocular pressure. RESULTS: There was no significant difference in achieving each intraocular pressure criterion between groups (12 months, P = 1.0; 24 months, P = 0.330). In the first 12 months, significantly more trabeculectomies in the Trab_phaco group failed, requiring additional intervention to control the IOP (39%) compared with the Phaco_trab (10%) group (P = 0.028). Although this trend continued at 24 months, there were no significant differences in failure rates (P = 0.522). CONCLUSIONS: Phacoemulsification performed after trabeculectomy significantly increased rates of bleb failure in the following 12 months but not at 24 months.

Bleb vascularity following post-trabeculectomy subconjunctival bevacizumab: a pilot study.

BACKGROUND: To determine whether postoperative subconjunctival bevacizumab significantly alters bleb vascularity. DESIGN: A randomized, prospective interventional study. PARTICIPANTS: Forty-three eyes from 39 patients were recruited, with 21 eyes randomized to subconjunctival injections of 5-fluorouracil, and 22 eyes to combined 5-fluorouracil/bevacizumab. METHODS: All patients who underwent uncomplicated primary antimetabolite augmented trabeculectomy who subsequently required postoperative subconjunctival 5-fluorouracil injection within 4 weeks of surgery were eligible. Patients were randomized to receive subconjunctival 5-fluorouracil only (7.5 mg/0.15 mL) or 5-fluorouracil plus bevacizumab (1.25 mg/0.05 mL). MAIN OUTCOME MEASURES: Primary outcome was bleb vascularity with secondary endpoints including visual acuity, intraocular pressure, bleb morphology, complications and total numbers of 5-fluorouracil injections were recorded at baseline, week 12 and 18 months. RESULTS: At week 12, there was no significant difference between groups for visual acuity, intraocular pressure, bleb vascularity and morphology, or total number of 5-fluorouracil injections. By 18 months, 47.4% of the 5-fluorouracil/bevacizumab group exhibited central bleb avascularity compared with 21.1% of the 5-fluorouracil group (Fisher's exact test, P = 0.17). Two bleb complications (one blebitis; one suture abscess) recorded in the 5-fluorouracil/bevacizumab group. CONCLUSIONS: After a single combined injection, a trend for increased central bleb avascularity was observed, although this effect was not sufficient to reach statistical significance. This, in addition to the occurrence of two bleb-related complications in the bevacizumab group, suggests the need for a larger clinical trial to further evaluate the safety and efficacy of bevacizumab as a modulating agent in glaucoma filtration surgery.

Australian and New Zealand Registry of Advanced Glaucoma: methodology and recruitment.

BACKGROUND: Glaucoma is a sight-threatening disease affecting 3% of the population over the age of 50. Glaucoma is treatable, and severe vision loss can usually be prevented if diagnosis is made at an early stage. Genetic factors play a major role in the pathogenesis of the condition, and therefore, genetic testing to identify asymptomatic at-risk individuals is a promising strategy to reduce the prevalence of glaucoma blindness. Furthermore, unravelling genetic risk factors for glaucoma would also allow a better understanding of the pathogenesis of the condition and the development of new treatments. DESIGN: The Australian and New Zealand Registry of Advanced Glaucoma is a prospective study that aims to develop a large cohort of glaucoma cases with severe visual field loss to identify novel genetic risk factors for glaucoma blindness. METHODS: Clinical information and blood are collected from participants after referral by eye practitioners. Samples are collected across Australia and New Zealand using postage kits. PARTICIPANTS: Our registry has recruited just over 2000 participants with advanced glaucoma, as well as secondary and developmental glaucomas. RESULTS: A positive family history of glaucoma is present in more than half of the advanced glaucoma cases and the age at diagnosis is significantly younger for participants with affected relatives, which reinforces the involvement of genetic factors in glaucoma. CONCLUSIONS: With the collection of glaucoma cases recruited so far, our registry aims to identify novel glaucoma genetic risk factors to establish risk profiling of the population and protocols for genetic testing.

Optic disc evaluation in optic neuropathies: the optic disc assessment project.

OBJECTIVE: Optic nerve morphology is affected by genetic and acquired disease. Glaucoma is the most common optic neuropathy; autosomal-dominant optic atrophy (ADOA) and Leber's hereditary optic neuropathy (LHON) are the most prevalent hereditary optic neuropathies. These 3 entities can exhibit similar topographical changes at the optic nerve head. Both ADOA and LHON have been reported to be misdiagnosed as glaucoma. Our aim was to determine whether glaucoma subspecialists and neuro-ophthalmologists can distinguish these diagnoses on optic disc assessment alone. DESIGN: Observational study. PARTICIPANTS: Twenty-three optic nerve experts. METHODS: We randomized and masked 60 high-resolution stereoscopic optic disc photographs (15 ADOA images, 15 LHON, 15 glaucoma, and 15 normal controls). Experts were asked to assess the discs on 12 conventional topographic features and assign a presumptive diagnosis. Intra- and interanalysis was performed using the index of qualitative variation and absolute deviation. MAIN OUTCOME MEASURES: Can glaucoma specialists and neuro-ophthalmologists distinguish among the disease entities by optic nerve head phenotype. RESULTS: The correct diagnosis was identified in 85%, 75%, 27%, and 16% of the normal, glaucoma, ADOA, and LHON disc groups, respectively. The proportion of correct diagnoses within the ADOA and LHON groups was significantly lower than both normal and glaucomatous (P<0.001). Where glaucoma was chosen as the most likely diagnosis, 61% were glaucomatous, 34% were pathologic but nonglaucomatous discs, and 5% were normal. There was greater agreement for individual parameters assessed within the normal disc set when compared with pathologic discs (P<0.05). The only parameter to have a significantly greater agreement within the glaucomatous disc set when compared with ADOA or LHON disc sets was pallor, whereby experts agreed on is absence in the glaucomatous discs but were not in agreement on its presence or its absence in the ADOA and LHON discs (P<0.01). CONCLUSIONS: Optic neuropathies can result in similar topographic changes at the optic disc, particularly in late-stage disease, making it difficult to differentiate ADOA and LHON from glaucoma based on disc assessment alone. Other clinical parameters such as acuity, color vision, history of visual loss, and family history are required to make an accurate diagnosis.

Glaucomatous optic neuropathy evaluation project: a standardized internet system for assessing skills in optic disc examination.

BACKGROUND: Development of a standardized internet-based system to self-assess skills in optic disc examination for glaucoma risk assessment. DESIGN: Prospective internet-based observational study. PARTICIPANTS: Total of 197 participants (glaucoma subspecialists, general ophthalmologists and trainees) from 22 countries. METHODS: Forty-two optic disc images demonstrating a range of features were selected from 2500 monoscopic disc photographs of normal and glaucomatous eyes. Images were presented to clinicians via website (http://www.gone-project.com). Participants were asked to assess nine topographic features and make a subjective assessment of glaucoma likelihood. MAIN OUTCOME MEASURES: Inter-observer agreement using kappa (κ) or weighted kappa (κ(w) ). RESULTS: There was substantial level of inter-observer agreement between glaucoma subspecialists for assessment of glaucoma likelihood (κ(w) = 0.63). Inter-observer agreement was high for haemorrhage (κ= 0.83) and substantial for disc size, disc shape, cup:disc ratio, peripapillary atrophy and cup shape (κ(w) = 0.59-0.68). Subspecialists had stronger inter-observer agreement for glaucoma likelihood and for most disc characteristics than did trainees: the greatest difference being the assessment for retinal nerve fibre layer loss. Analysis of individual disc answers from ophthalmology trainees showed that discs leading to lower agreement of glaucoma likelihood tend to produce lower agreement for the assessment of cup:disc ratio, cup shape, cup depth and retinal nerve fibre layer. Discs with features of moderate to deep cup or cup:disc ratio between 0.6 and 0.8 also lead to lower agreement in glaucoma likelihood. CONCLUSIONS: This internet-based system is a readily accessible and standardized tool, for clinicians globally, that permits self-assessment and benchmarking of skills in optic disc examination.

Combined diode laser cyclophotocoagulation and intravitreal bevacizumab (Avastin) in neovascular glaucoma.

BACKGROUND: Intravitreal injection of bevacizumab (Avastin) in eyes with neovascular glaucoma (NVG) has recently been shown to induce rapid regression of anterior segment neovascularization and has promise as adjunct treatment to diode laser cyclophotocoagulation (CPC) to control intraocular pressure (IOP). This study presents the outcome of concomitant treatment with CPC and intravitreal bevacizumab in painful poor visual potential eyes in a case series of consecutively diagnosed NVG. METHODS: Twelve patients (14 eyes) were treated with CPC and concurrent intravitreal bevacizumab 0.05 mL (1.25 mg) and study end-points were IOP lowering, regression of anterior segment neovascularization and resolution of pain. RESULTS: The mean preoperative IOP was 42.1 11.4 and was lowered to 16.6 7.1 mmHg at 1-month postoperatively. Anterior segment neovascularization regressed dramatically within 1 week of intravitreal bevacizumab in 12 eyes. Thirteen eyes reported persistent relief of ocular pain at 6 months following treatment. CONCLUSIONS: Combined intravitreal bevacizumab and CPC treatment for NVG provides rapid control of anterior segment neovascularization and may lead to improved symptomatic relief and IOP control.

The apolipoprotein epsilon4 gene is associated with elevated risk of normal tension glaucoma.

PURPOSE: Inheritance of a particular apolipoprotein E gene polymorphism, the epsilon4 allele, has been associated with elevated risk for Alzheimer's disease and a poor outcome following head injury. The neuronal injury associated with Alzheimer's disease and brain injury may have a number of similarities with the nerve cell changes associated with glaucoma. Thus, we have investigated the association of inheritance of apolipoprotein E allelic isoforms (epsilon2, [epsilon]3, and epsilon4) with relative risk for different forms of glaucoma. METHODS: Apolipoprotein E genotype was examined in a Tasmanian population sample comprised of glaucoma sufferers with elevated or normal intraocular pressure and compared to a control sample of elderly Tasmanians without glaucoma. RESULTS: Approximately twice as many normal tension (38.0%) and high tension (34.2%) glaucoma cases possessed an epsilon4 allele compared to control cases (18.9%). The odds of epsilon4 carriers having normal tension glaucoma were significantly greater than for epsilon3 homozygotes (odds ratio 2.45, 95% confidence interval [1.02-5.91]) even after adjusting for age and gender (odd ratio 2.87 [1.02-8.05]). The increased odds of high tension glaucoma among [epsilon]4 allele carriers were not significant (adjusted odds ratio 1.53 [0.64-3.68]). CONCLUSIONS: The data indicate that, in the Tasmanian population, inheritance of the [epsilon]4 allele is associated with elevated risk for glaucomatous changes that are not related to increased intraocular pressure.

Glaucoma phenotype in pedigrees with the myocilin Thr377Met mutation.

OBJECTIVE: To investigate the phenotype and age-related penetrance of primary open-angle glaucoma (POAG) in Australian families with the myocilin mutation Thr377Met. METHOD AND DESIGN: Cross-sectional genetic study. Four unrelated pedigrees carrying the Thr377Met mutation were ascertained from more than 2000 consecutive cases of POAG in the Glaucoma Inheritance Study in Tasmania and from families with glaucoma referred to the study from throughout Australia. Index cases and available family members were examined for signs of glaucoma, and the presence of the GLC1A Thr377Met mutation was ascertained by single-strand conformation polymorphism analysis and subsequent direct sequencing. RESULTS: From the 4 pedigrees carrying the Thr377Met mutation, 23 individuals with either ocular hypertension (OHT) or POAG were found, with a mean +/- SD age at diagnosis of 41.2 +/- 11.5 years, and a mean peak intraocular pressure of 31.7 +/- 9.9 mm Hg. A further 9 mutation carriers older than 18 years were studied who as yet showed no signs of OHT or POAG (6 of these 9 were younger than 30 years). A single individual with POAG was identified who did not carry the Thr377Met mutation. For Thr377Met carriers, age-related penetrance for OHT or POAG was 88% at age 30 years. A positive family history of POAG was present for 3 of the 4 index cases. Thirteen (57%) of the 23 Thr377Met carriers with OHT or POAG had undergone glaucoma drainage surgery. Although the glaucoma in these families appears to be pressure dependent, 2 individuals showed optic disc cupping before detected elevation in intraocular pressure. One family was of British origin, with a different background haplotype from the other 3 families from Greece or Macedonia, who shared a common haplotype. CONCLUSIONS: The GLC1A Thr377Met mutation is associated with POAG that, in the pedigrees studied, had a younger age at onset and higher peak intraocular pressure than in pedigrees with the more common Gln368STOP mutation. In addition, patients with glaucoma with the Thr377Met mutation were more likely to have undergone glaucoma drainage surgery.

Tonography demonstrates reduced facility of outflow of aqueous humor in myocilin mutation carriers.

PURPOSE: To demonstrate the effect in vivo of the myocilin gene mutation Thr377Met on outflow facility of aqueous humor, as measured by tonography. MATERIALS AND METHODS: Forty-two members of a pedigree known to carry the Thr377Met mutation were examined for glaucoma, evaluated with tonography, and screened for myocilin mutations. Tonography was used to calculate the coefficient of aqueous outflow facility (C), as well as the ratio of the resting intraocular pressure to C (P(0)/C). Subjects were reexamined for glaucoma 5 years after tonography. RESULTS: Seven subjects were excluded because of previous treatment known to alter facility of aqueous outflow. The mean outflow facility of the eyes of the 12 subjects carrying the Thr377Met mutation was significantly reduced compared with the 23 non-carriers' eyes using both C (P<0.001) and P(0)/C (P<0.001). Reduced outflow facility was also demonstrated in those mutation carriers who were not yet expressing clinical signs of glaucoma or ocular hypertension when measured using C (P = 0.015) and P(0)/C (P = 0.001). After 5 years, progression towards glaucoma had occurred in 5 of the myocilin mutation-carriers, 2 of whom showed bilateral progression; 3 carriers remained completely normal. Four subjects had bilateral glaucoma at the outset and remained unchanged. The carriers' eyes that progressed towards glaucoma had reduced outflow facility compared with those that remained normal, although the difference was not statistically significant. CONCLUSIONS: Carriers of the myocilin Thr377Met mutation have reduced outflow facility, which may be detected prior to developing glaucoma. Tonography was not seen to be clinically useful in predicting progression towards glaucoma.

Sticky eye, tricky diagnosis.

BACKGROUND: Infective conjunctivitis is common and mostly responds well to supportive management and/or empiric antibiotic treatment. At times the differential diagnosis includes more serious conditions that potentially threaten vision. Recurrence and treatment failures are relatively common. OBJECTIVE: To outline the usual clinical appearance of conjunctivitis and its management. To explore the clinical appearance (with the help of case studies) of conditions that have been mistaken for conjunctivitis, and to consider some of the conditions that may coexist that contribute to recurrence and nonresponsiveness. DISCUSSION: Empiric treatment for presumed bacterial conjunctivitis remains an appropriate course of action. Care must be taken in certain groups who are at high risk of complications. Careful review of the clinical appearance and consideration of other possible diagnoses is mandatory in nonresponding patients.

Glaucomatous optic neuropathy evaluation (GONE) project: the effect of monoscopic versus stereoscopic viewing conditions on optic nerve evaluation.

PURPOSE: To determine whether monoscopic vs stereoscopic viewing impacts evaluation of optic disc photographs for glaucoma diagnosis in an expert population. DESIGN: Prospective observational study. METHODS: Twenty pairs of high-quality monoscopic and stereoscopic photographs of similar size and magnification (ie, 40 images), were selected to demonstrate a range of optic disc features from a total of 197 eyes of 197 patients with glaucoma and normal subjects recruited from a tertiary clinic. These were presented in randomized order via an interactive platform (http://stereo.gone-project.com/). Participants assessed 9 topographic features and estimated glaucoma likelihood for each photograph. Main outcome measures were intra- and inter-observer agreement. RESULTS: There was good intra-observer agreement between monoscopic and stereoscopic assessments of glaucoma likelihood (κw = 0.56). There was also good to substantial agreement for peripapillary atrophy (κw = 0.65), cup shape (κw = 0.65), retinal nerve fiber layer loss (κw = 0.69), vertical cup-to-disc ratio (κw = 0.58), and disc shape (κw = 0.57). However, intra-observer agreement was only fair to moderate for disc tilt, cup depth, and disc size (κw = 0.46-0.49). Inter-observer agreement for glaucoma likelihood in monoscopic photographs (κw = 0.61, 95% confidence interval [CI] = 0.55-0.67) was substantial and not lower than in stereoscopic photographs (κw = 0.59, CI = 0.54-0.65). Monoscopic photographs did not lead to lower levels of inter-observer agreement compared to stereoscopic photographs in the assessment of any optic disc characteristics, for example disc size (mono κw = 0.65, stereo κw = 0.52) and cup-to-disc ratio (mono κw = 0.72, stereo κw = 0.62). CONCLUSIONS: For expert observers in the evaluation of optic disc photographs for glaucoma likelihood, monoscopic optic disc photographs did not appear to represent a significant disadvantage compared to stereoscopic photographs.

Glaucomatous optic neuropathy evaluation project: factors associated with underestimation of glaucoma likelihood.

IMPORTANCE: Glaucoma is a significant health problem for which diagnosis remains suboptimal. Optic disc evaluation, which is fundamental to the diagnosis, is a difficult skill to acquire. OBJECTIVES: To determine the optic disc characteristics that most influence decision making in the assessment of glaucoma likelihood and to ascertain the optic disc features associated with overestimation and underestimation of glaucoma likelihood. DESIGN, SETTING, AND PARTICIPANTS: This prospective, observational, Internet-based study with multinational participation included 197 ophthalmic clinicians (37 glaucoma subspecialists, 51 comprehensive ophthalmologists, and 109 ophthalmology trainees) from 22 countries who self-registered for the Glaucomatous Optic Neuropathy Evaluation (GONE) Project from December 1, 2008 through June 30, 2010. INTERVENTIONS: A series of 42 monoscopic optic disc photographs of healthy and glaucomatous eyes were presented to clinicians using the GONE Project Program. Participants were asked to assess each disc according to 9 conventional topographic features and assign a presumptive grade for glaucoma likelihood. MAIN OUTCOMES AND MEASURES: Agreement (κ and weighted κ) among participants for disc signs and glaucoma likelihood and contributions of disc-related factors to overestimation and underestimation of glaucoma likelihood. RESULTS: Ophthalmology trainees and comprehensive ophthalmologists underestimated glaucoma likelihood in a mean (SD) of 22.1% (1.6%) and 23.8% (1.8%) of discs, respectively. Underestimation of vertical cup-disc ratio and failure to identify retinal nerve fiber layer loss, disc hemorrhage, or rim loss were most likely to lead to underestimation of glaucoma. When all 4 features were inaccurately assessed, underestimation of glaucoma likelihood increased to 43.0%. Ophthalmology trainees and comprehensive ophthalmologists overestimated glaucoma likelihood in a mean (SD) of 13.0% (1.2%) and 8.9% (1.3%) of discs, respectively. Overestimation of glaucoma likelihood was associated with overestimation of retinal nerve fiber layer loss, rim loss, vertical cup-disc ratio, disc hemorrhage, and incorrect assessment of disc tilt and was more likely in large discs. CONCLUSIONS AND RELEVANCE: Ophthalmology trainees and comprehensive ophthalmologists underestimated glaucoma likelihood in approximately 1 in 5 disc photographs and were twice as likely to underestimate as overestimate glaucoma likelihood. Underestimating the vertical cup-disc ratio and cup shape and missing retinal nerve fiber layer defects and disc hemorrhage were the key errors that led to underestimation. When all 4 parameters were incorrectly assessed, underestimation increased to almost 1 in 2.

Intraocular pressure lowering is associated with an increase in the photopic negative response (PhNR) amplitude in glaucoma and ocular hypertensive eyes.

PURPOSE: The aim of our study was to determine whether IOP lowering in glaucomatous and ocular hypertensive (OHT) eyes leads to an improvement in the full-field photopic negative response (PhNR) of the electroretinogram. METHODS: A prospective nonrandomized interventional cohort study was conducted. Patients with OHT or glaucomatous optic neuropathy were recruited, and photopic full-field electroretinograms (ERG) were performed at baseline and then repeated 1 to 2 months later. The change in PhNR amplitude was compared between those eyes that had a significant lowering in IOP (defined as >25% decrease from baseline or to a predetermined target IOP) during follow-up and those that did not. RESULTS: From a cohort of 30 eyes, 18 eyes had a significant reduction in IOP during follow-up (n = 18) and 12 eyes had no significant change in IOP (<25% reduction in IOP, n = 12). A significant increase in PhNR amplitude and the PhNR/b-wave amplitude ratios was observed in the reduced IOP group, but not in the IOP stable group for the two flash intensities used (2.25 and 3.00 cd.s/m(2)). CONCLUSIONS: The full-field PhNR amplitude provides a potentially reversible measure of inner retinal function that improves after IOP lowering. Further study now is required to assess its use as a measure of optic nerve health in glaucoma patients.

A model to measure fluid outflow in rabbit capsules post glaucoma implant surgery.

PURPOSE: Prior models of glaucoma filtration surgery assess bleb morphology, which does not always reflect function. Our aim is to establish a model that directly measures tissue hydraulic conductivity of postsurgical outflow in rabbit bleb capsules following experimental glaucoma filtration surgery. METHODS: Nine rabbits underwent insertion of a single-plate pediatric Molteno implant into the anterior chamber of their left eye. Right eyes were used as controls. The rabbits were then allocated to one of two groups. Group one had outflow measurements performed at 1 week after surgery (n = 5), and group two had measurements performed at 4 weeks (n = 4). Measurements were performed by cannulating the drainage tube ostium in situ with a needle attached to a pressure transducer and a fluid column at 15 mm Hg. The drop in the fluid column was measured every minute for 5 minutes. For the control eyes (n = 6), the anterior chamber of the unoperated fellow eye was cannulated. Animals were euthanized with the implant and its surrounding capsule dissected and fixed in 4% paraformaldehyde, and embedded in paraffin before 6-µm sections were cut for histologic staining. RESULTS: By 7 days after surgery, tube outflow was 0.117 ± 0.036 µL/min/mm Hg at 15 mm Hg (mean ± SEM), whereas at 28 days, it was 0.009 ± 0.003 µL/min/mm Hg. Control eyes had an outflow of 0.136 ± 0.007 µL/min/mm Hg (P = 0.004, one-way ANOVA). Hematoxylin and eosin staining demonstrated a thinner and looser arrangement of collagenous tissue in the capsules at 1 week compared with that at 4 weeks, which had thicker and more densely arranged collagen. CONCLUSIONS: We describe a new model to directly measure hydraulic conductivity in a rabbit glaucoma surgery implant model. The principal physiologic endpoint of glaucoma surgery can be reliably quantified and consistently measured with this model. At 28 days post glaucoma filtration surgery, a rabbit bleb capsule has significantly reduced tissue hydraulic conductivity, in line with loss of implant outflow facility, and increased thickness and density of fibrous encapsulation.

Posterior revision for failed blebs: long-term outcomes.

AIM: To report the long-term efficacy and safety of same site revision trabeculectomy with mitomycin application via a posterior approach. METHODS: A noncomparative retrospective case series of consecutive revision trabeculectomies performed for inadequate bleb function between March 2003 and March 2007 by a single surgeon. Surgery involved a posterior/fornix incision with opening of the scleral flap posteriorly at the same site as previous surgery and application of 0.2 to 0.4 mg/mL mitomycin. RESULTS: Fifty-seven eyes were followed for an average of 33 ± 15 months. Mean baseline intraocular pressure (IOP) reduced from 21.5 ± 6.5 to 11.2 ± 4.4 and 8 ± 3.6 mm Hg at 1 and 5 years, respectively (P<0.001). On Kaplan-Meier survival analysis the probability of maintaining IOP ≤ 15 mm Hg without medication at the end of 1 year was 95% (n=57) and at 3 (n=36) and 5 years (n=7) was 84%. Eighty-five percent of patients were on no antiglaucoma drops at last follow-up. Four cases required a second procedure (7%), transient choroidal effusions occurred in 4 eyes (7%), corneal decompensation in 1 eye (1.7%), and ptosis in 1 (1.7%). CONCLUSIONS: Posterior approach to surgical revision of failed filtration surgery is an effective procedure with good long-term control of IOP.

Gaze behavior among experts and trainees during optic disc examination: does how we look affect what we see?

PURPOSE: The authors compared the visual gaze behaviors of glaucoma subspecialists with those of ophthalmology trainees during optic disc and retinal nerve fiber layer (RNFL) examination. METHODS: Seven glaucoma subspecialists and 23 ophthalmology trainees participated in the project. Participants were shown eight glaucomatous optic disc images with varied morphology. Eye movements during examination of the optic disc photographs were tracked. For each disc image, graders were asked to assign a presumptive diagnosis for probability of glaucoma. There was no time restriction. RESULTS: Overall, trainees spent more time looking at disc images than glaucoma subspecialists (21.3 [13.9-37.7] vs. 16.6 [12.7-19.7]) seconds; median [interquartile range (IQR)], respectively; P < 0.01) and had no systematic patterns of gaze behavior, and gaze behavior was unaltered by disc morphology or topographic cues of pathology. Experienced viewers demonstrated more systematic and ordered gaze behavior patterns and spent longer times observing areas with the greatest likelihood of pathology (superior and inferior poles of the optic nerve head and adjacent RNFL) compared with the trainees. For discs with focal pathology, the proportion of total time spent examining definite areas of pathology was 28.9% (22.4%-33.6%) for glaucoma subspecialists and 13.5% (12.2%-19.2%) for trainees (median [IQR]; P < 0.05). Furthermore, experts adapted their viewing habits according to disc morphology. CONCLUSIONS: Glaucoma subspecialists adopt systematic gaze behavior when examining the optic nerve and RNFL, whereas trainees do not. It remains to be elucidated whether incorporating systematic viewing behavior of the optic disc and RNFL into teaching programs for trainees may expedite their acquisition of accurate and efficient glaucoma diagnosis skills.