Gray Optic Disc Crescent: Evaluation of Anatomic Correlate by Spectral-Domain OCT.

PURPOSE: To test the hypothesis that the anatomic correlate of the gray optic disc crescent is pigmentation of externally oblique border tissue of Elschnig. DESIGN: Retrospective study. PARTICIPANTS: African-American adult men with or without clinically apparent gray optic disc crescents. METHODS: McNemar's test for paired data and kappa statistic with 95% confidence intervals were used to examine the relationships between eyes with or without gray optic disc crescents and corresponding spectral-domain (SD) OCT images with enhanced depth imaging (EDI). MAIN OUTCOME MEASURES: Correlation between clinical gray optic disc crescents and hyperreflectivity of externally oblique border tissue of Elschnig by SD OCT with EDI. RESULTS: Twenty-five eyes had clinically apparent gray optic disc crescents, of which SD OCT with EDI revealed hyperreflectivity (interpreted as increased pigmentation) of externally oblique (obtuse angle) border tissue of Elschnig in 22 eyes, that is, extending into Bruch's membrane opening and presumably visible by funduscopy. Thirty-two eyes from matched participants had no apparent gray optic disc crescent, of which SD OCT with EDI revealed hyperreflectivity of the border tissue of Elschnig in 23 eyes, but with a nonoblique (right angle) or internal (acute angle) angle, which would presumably obstruct funduscopic visualization. CONCLUSIONS: Observations by SD OCT with EDI suggest that the anatomic correlate of the gray optic disc crescent is pigmentation of externally oblique border tissue of Elschnig.

In vitro characteristics of Tenon's fibroblast lines derived from pediatric and adult eyes do not fully explain pediatric glaucoma surgery failure: a preliminary report.

PURPOSE: To compare the in vitro characteristics of Tenon's capsule fibroblasts from children and adults that may be relevant to filtration surgery success. METHODS: Fibroblast cell lines derived from 5 young (median patient age, 2.4 years) and 7 old (median patient age, 71 years) discarded Tenon's capsule surgical specimens were used at early passage (P2-P3). Fibroblasts were plated at "high" (10(4)cells/cm(2)) or "low" density (10(3)cells/cm(2)) and harvested at days 0-14, for growth curve and doubling time comparisons. Migration was measured using a wound model (confluent monolayers ± 5-fluorouracil [5-FU] over 1-96 hours). Collagen synthesis was measured as secreted hydroxyproline/24 hours from confluent monolayers. RESULTS: At low density, "young" fibroblasts achieved higher cell numbers at confluence (day 14) compared with "old": 158 ± 35 versus 105 ± 12 × 10(3)cells/cm(2) (P = 0.0034). Mean doubling time for young versus old was similar at low density plating: 20.95 ± 1.55 versus 22.37 ± 2.09 hours (P = 0.26). It was shorter, however, for young versus old at high-density plating: 42.11 ± 6.01 versus 54.26 ± 4.24 hours (P = 0.0051). Wound closure rates were similar for young versus old cells (4 lines for each group) with and without 5-FU. Collagen synthesis was similar for young and old (4 lines for each group). CONCLUSIONS: Although young fibroblasts reached higher density than old at confluence and had shorter doubling times at high-density plating, wound closure/migration and collagen synthesis rates were similar. Despite the preliminary nature of this study (few specimens, limited cell features explored), factors besides those intrinsic to the fibroblasts themselves likely mediate the more rapid healing/scarring after glaucoma filtration surgery in children.

In vitro and in vivo comparison of two suprachoroidal shunts.

PURPOSE: To compare fibrosis, aqueous humor dynamics, and intraocular pressure (IOP) of two suprachoroidal shunts as part of a new class of glaucoma drainage devices. METHODS: Following proliferation analysis in vitro, 20 rabbits were implanted with either a gold shunt (GS, GMSplus+, SOLX) or a polypropylene shunt (PS, Aquashunt, OPKO). Ten eyes received mitomycin C (MMC) and triamcinolone. Peak and trough IOP were monitored with a pneumatonometer and tono-pen for 15 weeks. Aqueous humor dynamics were evaluated fluorophotometrically and tonographically. Fibrosis was quantified. RESULTS: In vitro proliferation was similar. In vivo, both shunts were devoid of foreign body reaction but exhibited fibrosis, and GS showed vascularization. There was no significant difference in aqueous or uveoscleral flow. Preoperative morning IOP was 23.7 ± 2 mm Hg, and evening IOP was 26.5 ± 2 mm Hg (P = 0.000). Morning IOP was decreased through 15 weeks and evening IOP through 8 weeks in all groups. The morning IOP decrease was most profound at 15 weeks in PS (41%) compared to GS (18%). Antifibrotics initially enhanced but eventually diminished shunt performance. At 15 weeks, thickness of scleral fibrosis was greater in GS (246 ± 47 µm) and PS (188 ± 47 µm, P = 0.285) compared with GS+MMC (109 ± 26 µm, P = 0.023 to GS) and PS+MMC (48 ± 30 µm, P = 0.028 to PS). CONCLUSIONS: In a rabbit model, suprachoroidal polypropylene and gold shunts allow access to a new drainage pathway with different IOP profiles that can be modified with antifibrotics.

Evaluation of adverse events in self-reported sulfa-allergic patients using topical carbonic anhydrase inhibitors.

PURPOSE: To investigate whether a self-reported history of allergy to sulfa-based drugs is a predictor for subsequent adverse reactions to topical carbonic anhydrase inhibitors (CAIs). METHODS: A retrospective case-controlled cohort study via chart review was performed on 1,287 patients with a diagnosis of glaucoma. The outcome measure was the development of an adverse reaction (either ocular, systemic, or both) within at least 30 days after receipt of 1 of 4 classes of topical glaucoma medications: CAIs (dorzolamide and brinzolamide), prostaglandin analogues, beta-adrenergic blockers, and alpha2-adrenergic agonists. RESULTS: Patients with a self-reported history of sulfa allergy had significantly more ocular adverse reactions after the initiation of any of the topical antiglaucoma medications when compared to those patients with no reported allergies. Patients with a self-reported sulfa allergy and patients who self-reported other, nonsulfa-related allergies had similar rates of adverse reactions to most of the topical medications. The patients reporting a sulfa allergy who used topical CAIs did not have more adverse reactions compared with patients who reported having other, nonsulfa-related allergies who used topical CAIs. Self-reported sulfa-allergic patients had similar rates of adverse reactions to topical CAIs compared with topical prostaglandin analogues. CONCLUSION: It may be safe to use a topical CAI in patients who report a history of a sulfa allergy. Patients with medication allergies of any kind may be more likely to develop allergic reactions to other, unrelated drug classes.

Elevation of intraocular pressure in glaucoma patients after automated visual field testing.

PURPOSE: To examine whether automated visual field (VF) testing may exert a short-term influence on subsequent intraocular pressure (IOP) measurement during the same visit. METHODS: We reviewed patients with primary open-angle glaucoma whose most recent visit occurred at a major academic institution from July to December 2009 and who had 3 visits without intervening changes in glaucoma management within the previous 5 years. Exclusion criteria were patient admittance of nonadherence with medical therapy and documented difficulty of IOP measurement. One hundred nine right eyes from 109 patients were included. IOP obtained within 30 minutes after VF testing was compared with IOP from the previous and next visits without VF testing. Subgroup analyses included the role of reliability of VF test performance, surgical versus medical IOP control, and different topical medications. RESULTS: The average IOP measured after VF testing was 14.9 ± 4.7 mm Hg, higher than both the previous (13.7 ± 4.4 mm Hg, P < 0.001) and next visits without VF examination (13.8 ± 4.4 mm Hg, P < 0.001). A total of 22.9% of patients experienced a more than 20% increase of IOP. Eyes with surgical control had less IOP elevation than eyes with medical control (3.1% ± 15.9% vs. 11.7% ± 17.4%, P = 0.009). Users of ß-blockers or α-2-agonists had less IOP elevation than eyes controlled with prostaglandins or carbonic anhydrase inhibitors (0.9% ± 15.1% vs. 9.0% ± 12.3%, P = 0.030). CONCLUSIONS: This retrospective study suggests that patients with primary open-angle glaucoma experience a small and transient increase in IOP after VF testing and that this effect may be lower after surgical pressure control.

Glaucoma and systemic diseases.

Glaucoma management may be extremely challenging, especially in elderly patients who have a variety of systemic diseases and take multiple medications. We obtained a comprehensive medical history in patients with primary open-angle glaucoma to determine which systemic diseases are most prevalent and which systemic medications are most commonly used. We have also reviewed the literature that addresses how these concomitant diseases and medical treatments influence the management of glaucoma. Knowledge of systemic diseases and potential drug interactions, especially between various systemic and glaucoma medications, is important for the safe management of glaucoma patients.

Does titration of mitomycin C as an adjunct to trabeculectomy significantly influence the intraocular pressure outcome?

PURPOSE: To evaluate the benefit of titrating the concentration and exposure time of mitomycin C (MMC) as an adjunct to trabeculectomy. METHODS: This report consists of a retrospective study and a review of the literature. In the study, consecutive glaucoma patients were evaluated who underwent trabeculectomy with adjunctive MMC that was titrated for concentration and exposure time, based on patient's risk factors for surgical failure. After minimum follow-up of 6 months, patients were divided into success (intraocular pressure 7-17 mmHg), hypertension (>17 mmHg) and hypotony (<7 mmHg) groups, which were compared with regard to MMC protocol and patient variables. The literature review included reports of trabeculectomy and adjunctive MMC with and without titration. RESULTS: One hundred and fifty-five eyes of 155 patients were studied. There were no significant differences between the three outcome groups and MMC protocol (p > 0.05). The only significant patient variable was older age in the hypotony group (p = 0.009). The literature is conflicting regarding the value of titrating MMC as an adjunct in trabeculectomy. CONCLUSION: The outcome of trabeculectomy with adjunctive MMC appears to represent a complex interaction of patient and surgical variables. While there is some support for a benefit of titrating MMC according to individual patient variables, there is inadequate evidence at the present time to claim superiority for any MMC protocol, with or without titration.

Assessment of optic nerve cup-to-disk ratio changes in patients receiving multiple intravitreal injections of antivascular endothelial growth factor agents.

PURPOSE: To assess whether the transient intraocular pressure rise, frequent intraocular pressure fluctuations, or antivascular endothelial growth factor (VEGF) effects of repeated intravitreal injection of anti-VEGF agents can lead to changes in the optic nerve vertical cup-to-disk ratio (C/D). METHODS: Patients with a known history of glaucoma and those receiving triamcinolone acetonide were excluded from the study. Fundus photographs were cropped to optic disk images only, which were then randomized and independently graded by two glaucoma specialists. In patients who received treatments in only one eye, the fellow eye was used as a control. RESULTS: Twenty-three eyes of 21 patients met inclusion criteria. The mean change in C/D was -0.012 (95% confidence interval [CI], -0.053 to 0.029) for the treated group and -0.006 (95% CI, -0.106 to 0.095) for the control group, with no statistically significant difference (P = 0.90). The mean change in C/D for eyes receiving < or =5 injections (n = 9) was 0.003 (95% CI, -0.089 to 0.095) in the treated group and 0.054 (95% CI, -0.033 to 0.142) in the control group, with no statistically significant difference (P = 0.33). In eyes receiving >5 injections (n = 14), the mean change in C/D was -0.021 (95% CI, -0.095 to 0.052) in the treated group and -0.057 (95% CI, -0.231 to 0.116) in the control group, with no statistically significant difference (P = 0.70). CONCLUSION: There was no statistically significant change in the vertical C/D of optic nerves in patients receiving multiple intravitreal injections of anti-VEGF agents, regardless of whether they received fewer or more than five total injections. This suggests that the short-term intraocular pressure rise and frequent intraocular pressure fluctuation, as well as the anti-VEGF properties of these drugs, do not adversely change the optic nerve C/D. Additional prospective studies are warranted to confirm these conclusions.

Side effects associated with prostaglandin analog therapy.

Topical prostaglandin analogs, which have become first-line therapy in the medical management of glaucoma, have an excellent safety profile with regard to systemic side effects, but are associated with several ocular side effects. Some of these are common, with no apparent serious consequences other than cosmetic, whereas others are much less common but represent potentially sight-threatening side effects. The former group includes conjunctival hyperemia, elongation and darkening of eyelashes, induced iris darkening, and periocular skin pigmentation. The latter group of side effects, which are relatively rare and lack definitive causal relationship to prostaglandin analog therapy, includes iris cysts, cystoid macular edema, anterior uveitis, and reactivation of herpes simplex keratitis. Most of the literature regarding side effects associated with prostaglandin analogs involves the use of latanoprost, probably because it was the first to be studied. There is no evidence, however, aside from less conjunctival hyperemia with latanoprost, that the commercially available prostaglandin analogs differ significantly with regard to side effects.

Predicting response to glaucoma therapy in one eye based on response in the fellow eye: the monocular trial.

OBJECTIVE: To evaluate whether the change in intraocular pressure (IOP) observed in one eye after starting a glaucoma medication regimen is predictive of the change in IOP due to the same medication in the fellow eye. METHODS: A retrospective medical record review of 22 patients with primary open-angle glaucoma (POAG) and 27 glaucoma suspects who underwent monocular drug trials before the drug was added to the second eye. The absolute change in IOP from baseline and the relative change (change in treated eye minus change in fellow eye) in the first eye treated were compared with the second eye after binocular treatment. RESULTS: The absolute and relative decreases in IOP of the first eye were poorly correlated with those of the second eye in patients with POAG (r(2) < 0.001; P = .97 and r(2) = 0.040; P = .38, respectively). However, they were well correlated in glaucoma suspects (r(2) = 0.348; P = .001 and r(2) = 0.396; P < .001, respectively). CONCLUSIONS: The change in IOP of one eye due to a medication may be predictive of the subsequent response of the fellow eye to the same medication in glaucoma suspects, but not in patients with POAG. Using the fellow eye as a control may confer a more accurate portrayal of the true therapeutic effects of a medicine, although further study is needed to support both of these findings.

Normal-tension glaucoma: is it different from primary open-angle glaucoma?

PURPOSE OF REVIEW: Normal-tension glaucoma (NTG) is a common form of open-angle glaucoma throughout the world, and yet there are many unanswered questions regarding both the mechanisms of the optic neuropathy and the treatment of these patients. The present review considers how recent literature advances our understanding of both the mechanisms of glaucomatous damage and the treatment of patients with NTG. RECENT FINDINGS: The main theme in the current literature continues to be that NTG and primary open-angle glaucoma (POAG) represent a continuum of open-angle glaucomas, in which a certain level of intraocular pressure (IOP) is the predominant causative risk factor in POAG, while additional IOP-independent factors take increasing importance in NTG. There is considerable overlap between the two conditions, however, and within the population of NTG patients there are subsets in which IOP, blood flow and other factors assume relative importance. SUMMARY: In clinical practice, control of IOP remains the mainstay of managing NTG patients, but consideration must also be given to other factors, especially those that may influence perfusion of the optic nerve head. Treatment paradigms will likely change as researchers continue to investigate the mechanisms of glaucomatous optic neuropathy and search for IOP-independent neuroprotective agents.

Retinal arterial macroaneurysm with blood-staining of the internal limiting membrane and optic nerve.

An 83-year-old man presented with a retinal arterial macroaneurysm complicated by vitreous hemorrhage, hyphema and ghost cell glaucoma requiring surgical intervention. After pars plana vitrectomy, anterior chamber wash-out and laser photocoagulation, the retinal arterial macroaneurysm closed but blood-staining of the optic nerve, internal limiting membrane and peripapillary vessels persisted. The rare sequela of blood-staining, which in this case did not adversely affect the final visual outcome, further contributes to our understanding of the wide ranging clinical spectrum of retinal arterial macroaneurysms.

Novel pressure-to-cornea index in glaucoma.

BACKGROUND: Several conversion tables and formulas have been suggested to correct applanation intraocular pressure (IOP) for central corneal thickness (CCT). CCT is also thought to represent an independent glaucoma risk factor. In an attempt to integrate IOP and CCT into a unified risk factor and avoid uncertain correction for tonometric inaccuracy, a new pressure-to-cornea index (PCI) is proposed. METHODS: PCI (IOP/CCT(3)) was defined as the ratio between untreated IOP and CCT(3) in mm (ultrasound pachymetry). PCI distribution in 220 normal controls, 53 patients with normal-tension glaucoma (NTG), 76 with ocular hypertension (OHT), and 89 with primary open-angle glaucoma (POAG) was investigated. PCI's ability to discriminate between glaucoma (NTG+POAG) and non-glaucoma (controls+OHT) was compared with that of three published formulae for correcting IOP for CCT. Receiver operating characteristic (ROC) curves were built. RESULTS: Mean PCI values were: Controls 92.0 (SD 24.8), NTG 129.1 (SD 25.8), OHT 134.0 (SD 26.5), POAG 173.6 (SD 40.9). To minimise IOP bias, eyes within the same 2 mm Hg range between 16 and 29 mm Hg (16-17, 18-19, etc) were separately compared: control and NTG eyes as well as OHT and POAG eyes differed significantly. PCI demonstrated a larger area under the ROC curve (AUC) and significantly higher sensitivity at fixed 80% and 90% specificities compared with each of the correction formulas; optimum PCI cut-off value 133.8. CONCLUSIONS: A PCI range of 120-140 is proposed as the upper limit of "normality", 120 being the cut-off value for eyes with untreated pressures or=22 mm Hg. PCI may reflect individual susceptibility to a given IOP level, and thus represent a glaucoma risk factor. Longitudinal studies are needed to prove its prognostic value.

Iridocorneal endothelial syndrome in a child.

The iridocorneal endothelial syndrome is an important and unusual cause of acquired glaucoma in adults. We report its occurrence in a child who presented with glaucoma. The patient required glaucoma surgery, and a goniotomy and trabeculectomy were performed. The patient's clinical findings and the results of surgeries are described.

Factors associated with failure to follow up after glaucoma screening: a study in an African American population.

PURPOSE: To evaluate variables associated with failure to access free eye care after participating in glaucoma screening. DESIGN: Review of responses to a survey completed by participants during glaucoma screening. PARTICIPANTS: Two hundred seventy-three surveys completed by participants of African descent during screening. METHODS: African Americans 40 years or older participated in community glaucoma screening clinics, which included a survey with demographic and social variables. Each participant was given a preliminary diagnosis and encouraged to attend a free eye clinic for a complete examination. Survey results were correlated with attendance at the follow-up examination, using Student's t test, chi-square test, and logistic regression analysis. MAIN OUTCOME MEASURE: Noncompliance with follow-up after glaucoma screening. RESULTS: When adjusting for risk factors in logistic regression analysis, noncompliance was associated with living alone (P = 0.008), smoking (P = 0.0005), and lacking a car (P<0.01). Odds of noncompliance for participants living alone were 2.2 times higher than those for participants not living alone. Odds of noncompliance for participants who smoked were 3.0 times greater than those for participants who did not smoke. Odds of noncompliance for participants who did not have access to a car for their last eye examination were 2.1 times greater than those for participants who did. CONCLUSION: Socioeconomic factors such as smoking, lack of access to a car for eye examinations, and living alone are associated with noncompliance to follow-up after glaucoma screening clinics. Identifying persons with these variables may facilitate improved compliance.