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Papers by George Cioffi

PURPOSE. To evaluate electrophysiologic function in glaucoma by using a new stimulus designed to ... more PURPOSE. To evaluate electrophysiologic function in glaucoma by using a new stimulus designed to enhance ganglion cell and optic nerve head component (ONHC) contributions to multi- focal electroretinogram (mfERG) responses. METHODS. mfERGs of 16 individuals with glaucoma (POAG) and 18 normal control subjects were recorded and analyzed with a VER imaging system. The stimulus had three frames inserted between each

Optometry and Vision Science, 1999

To assess whether smaller targets and a 24-2 stimulus presentation pattern would improve the abil... more To assess whether smaller targets and a 24-2 stimulus presentation pattern would improve the ability of frequency doubling technology (FDT) perimetry to detect and characterize early glaucomatous visual field loss. One hundred normal subjects between the ages of 20 and 85 participated in this study. In addition, 53 patients who either had early glaucomatous visual field loss (n = 23) or were high-risk glaucoma suspects with normal conventional visual fields (n = 30) were evaluated with the commercial version of FDT perimetry (full threshold test) with 17 stimuli (four 10 degrees diameter square targets per quadrant and a central 5 degrees circular target) and a custom version of FDT perimetry using 54 stimuli (4 degrees targets with 6 degrees grid spacing) arranged in a 24-2 stimulus presentation pattern. The custom FDT test using a 24-2 stimulus presentation pattern had a similar dynamic range, and demonstrated normal aging characteristics and test-retest reliability that were similar to the commercial version of FDT perimetry using 17 larger stimuli. Both FDT tests showed an age-related sensitivity reduction of approximately 0.6 dB per decade, and exhibited an average test-retest reliability of 1 to 1.5 dB. The custom 24-2 FDT perimetry test had a greater variation of sensitivity with eccentricity than the commercial version of FDT perimetry that was probably related to the difference in stimulus size. The custom 24-2 FDT perimetry test had a greater percentage of abnormal test locations than the commercial FDT test for both early glaucomas and high-risk glaucoma suspects. FDT perimetry can be performed with smaller targets using a presentation pattern that is similar to conventional automated perimetry. In comparison to the commercially available 17 target display, the 24-2 stimulus pattern appears to have modestly higher sensitivity for detection of early glaucomatous loss and provides better characterization of the pattern of visual field loss, but the test takes approximately twice as long.

Journal of Neuro-ophthalmology, 1996

Methyl methacrylate vascular corrosion casting techniques were used to examine the normal anterio... more Methyl methacrylate vascular corrosion casting techniques were used to examine the normal anterior optic nerve microvasculature in 18 human eye bank eyes. Selective cannulation of the central retinal artery, the short posterior ciliary arteries, or both, allowed the methyl methacrylate to be injected into the anterior optic nerve circulation. Preflushing with tissue plasminogen activator greatly enhanced the filling of the fine microvasculature by dissolving the intraluminal clots. The superficial nerve fiber layer of the optic nerve received its primary blood supply from the central retinal artery. In 11 of 13 eyes injected with methyl methacrylate through the short posterior ciliary arteries, there was a perineural, circular arterial anastomosis (circle of Zinn-Haller) at the scleral level. Branches from this circle penetrated the optic nerve to supply the prelaminar and laminar regions and the peripapillary choroid. In the two eyes without this arterial circle, direct branches from the short posterior ciliary arteries supplied the anterior optic nerve. The venous drainage of the anterior optic nerve was almost entirely through the central retinal vein and its tributaries. This study demonstrates that the main arterial vascular supply to the anterior optic nerve is from the short posterior ciliary arteries. The contribution of the peripapillary choroid to the anterior optic nerve is minimal in comparison to the direct contribution from the short posterior ciliary arteries.

JAMA Ophthalmology, 2015

Understanding factors that lead to nonadherence to glaucoma treatment is important to diminish gl... more Understanding factors that lead to nonadherence to glaucoma treatment is important to diminish glaucoma-related disability. To determine whether the implementation of the Medicare Part D prescription drug benefit affected rates of cost-related nonadherence and cost-reduction strategies in Medicare beneficiaries with and without glaucoma and to evaluate associated risk factors for such nonadherence. Serial cross-sectional study using 2004 to 2009 Medicare Current Beneficiary Survey data linked with Medicare claims. Coding to extract data started in January 2014 and analyses were performed between September and November of 2014. Participants were all Medicare beneficiaries, including those with a glaucoma-related diagnosis in the year prior to the collection of the survey data, those with a nonglaucomatous ophthalmic diagnosis in the year prior to the collection of the survey data, and those without a recent eye care professional claim. Effect of the implementation of the Medicare Part D drug benefit. The change in cost-related nonadherence and the change in cost-reduction strategies. Between 2004 and 2009, the number of Medicare beneficiaries with glaucoma who reported taking smaller doses and skipping doses owing to cost dropped from 9.4% and 8.2% to 2.7% (P < .001) and 2.8%, respectively (P = .001). However, reports of failure to obtain prescriptions owing to cost did not improve in the same period (3.4% in 2004 and 2.1% in 2009; P = .12). After Part D, patients with glaucoma had a decrease in several cost-reduction strategies, namely price shopping (26.2%-15.2%; P < .001), purchasing outside the United States (6.9%-1.3%; P < .001), and spending less money to save for medications (8.0% to 3.5%; P < .001). Using a multivariate analysis, the main independent risk factors common to all cost-related nonadherence measures were female sex, younger age, lower income (<$30 000), self-reported visual disability, and a smaller Lawton index. After the implementation of Part D, there was a decrease in the rate that beneficiaries with glaucoma reported engaging in cost-saving measures. Although there was a decline in the rate of several cost-related nonadherence behaviors, patients reporting failure to fill prescriptions owing to cost remained stable. This suggests that efforts to improve cost-related nonadherence should focus both on financial hardship and medical therapy prioritization, particularly in certain high-risk sociodemographic groups.

Seminars in ophthalmology, 2000

This article reviews the relationships between structural changes and visual function losses prod... more This article reviews the relationships between structural changes and visual function losses produced by glaucomatous damage. Structural characteristics of the optic nerve head and retinal nerve fiber layer include both qualitative and semi-quantitative clinical assessment methods as well as quantitative imaging techniques. Visual function properties include standard (white-on-white) automated perimetry and new techniques such as short wavelength automated perimetry and motion displacement threshold perimetry. Previous investigations consistently report a significant relationship between structural and functional deficits in glaucoma, with structural changes usually being reported to occur earlier than functional losses. In cases of focal damage, there appears to be a good topographic relationship between structural and functional losses. Several optic nerve head and retinal nerve fiber layer measures are reported to be good predictors of glaucomatous visual field loss. However, pre...

Archives of ophthalmology, 2005

To determine whether baseline confocal scanning laser ophthalmoscopy (CSLO) optic disc topographi... more To determine whether baseline confocal scanning laser ophthalmoscopy (CSLO) optic disc topographic measurements are associated with the development of primary open-angle glaucoma (POAG) in individuals with ocular hypertension. Eight hundred sixty-five eyes from 438 participants in the CSLO Ancillary Study to the Ocular Hypertension Treatment Study with good-quality baseline CSLO images were included in this study. Each baseline CSLO parameter was assessed in univariate and multivariate proportional hazards models to determine its association with the development of POAG. Forty-one eyes from 36 CSLO Ancillary Study participants developed POAG. Several baseline topographic optic disc measurements were significantly associated with the development of POAG in both univariate and multivariate analyses, including larger cup-disc area ratio, mean cup depth, mean height contour, cup volume, reference plane height, and smaller rim area, rim area to disc area, and rim volume. In addition, cla...

Documenta ophthalmologica. Advances in ophthalmology, 2002

While elevated intraocular pressure (IOP) undoubtedly plays a crucial role in many glaucoma patie... more While elevated intraocular pressure (IOP) undoubtedly plays a crucial role in many glaucoma patients, vascular dysregulation and chronic regional ischemia are also thought to contribute to the pathophysiology of glaucoma. In an effort to critically evaluate hypotheses involving vascular abnormalities in glaucoma, Cioffi, Van Buskirk and co-workers have developed a model of optic neuropathy based on chronic regional ischemia. The multifocal electroretinogram (MERG) has previously been used to assess function in non-human primates with experimental glaucoma induced by high-IOP. In this study, the MERG was used to monitor function in macaque monkeys with experimental glaucoma induced by chronic anterior optic nerve ischemia. Initial recordings from experimental eyes, which were later documented histologically to have moderate axon loss, revealed little difference from recordings of control eyes. This suggested that many of the signal components in the macaque MERG, which are known (fro...

Investigative ophthalmology & visual science, 2002

Glial cells are structurally and functionally linked to neuronal tissues. Pathologically, the cel... more Glial cells are structurally and functionally linked to neuronal tissues. Pathologically, the cells may be activated and characterized by increased size and number and altered cellular properties. In glaucoma, pathologic mechanisms within the anterior optic nerve may include glial activation. This study examines morphologic changes of glial cells in the retinas of glaucomatous eyes compared with age-matched control retinas. Paraffin-processed or flatmounted retinas from 17 human donor eyes [7 normal (donor age, 87.3 +/- 8.3 years) and 10 glaucomatous (donor age, 87.1 +/- 6.9 years)] were examined. With immunohistochemical methods, retinal glial cells were stained with an antibody to glial fibrillary acidic protein (GFAP). The morphology of the glial cells in normal and glaucomatous retinas was evaluated with fluorescence microscopy. Three types of glial cells were identified in flatmounted retinas with differing distributions in the peripapillary region, the nerve fiber layer (NFL),...

Archives of ophthalmology, 1998

To develop a brief symptom survey specific for persons with glaucoma, the Glaucoma Symptom Scale ... more To develop a brief symptom survey specific for persons with glaucoma, the Glaucoma Symptom Scale (GSS). Cross-sectional study of symptoms, functional impairment, and vision-targeted health-related quality of life among persons with glaucoma. A sample of 147 persons with glaucoma among a broad range of treatment categories from 4 tertiary care glaucoma centers and 44 persons without eye disease enrolled from the same 4 centers. Participants completed a modified version of the Ocular Hypertension Treatment Study 10-item symptom checklist. Participants also completed 2 vision-specific measures, the National Eye Institute Visual Function Questionnaire and the VF-14. Participants underwent a clinical evaluation, including ocular and medical history, dilated ophthalmic examination, and Humphrey 24-2 automated visual field testing. The GSS has 2 underlying domains that demonstrate sufficient internal consistency reliability for between-group comparisons. The GSS discriminates well between ...

Translational Vision Science & Technology, 2015

Citation: Susanna Jr R, De Moraes CG, Cioffi GA, Ritch R. Why do people (still) go blind from gla... more Citation: Susanna Jr R, De Moraes CG, Cioffi GA, Ritch R. Why do people (still) go blind from glaucoma? Trans Vis Sci Tech. 2015;4(1): 10, http://tvstjournal.org/doi/full/

JAMA ophthalmology, Jan 5, 2015

The Tube vs Trabeculectomy Trial (TVT) found that the 350-mm2 Baerveldt implant (tube) and trabec... more The Tube vs Trabeculectomy Trial (TVT) found that the 350-mm2 Baerveldt implant (tube) and trabeculectomy with mitomycin may be similarly effective in lowering intraocular pressure in primary open-angle glaucoma. However, to date, there are no published long-term clinical data on the cost-effectiveness of trabeculectomy with mitomycin vs tube insertion. To assess the cost-effectiveness of these procedures compared with maximal medical treatment. We used the Markov cohort model with a 5-year time horizon to study a hypothetical cohort of 100 000 patients who required glaucoma surgery. Quality-adjusted life-years (QALYs) gained, costs from the societal perspective, and the incremental cost-effectiveness ratio of medical treatment, trabeculectomy, and tube insertion. Costs were identified from Medicare Current Procedural Terminology and Ambulatory Payment Classification reimbursement codes and Red Book medication costs. The QALYs were based on visual field and visual acuity outcomes. T...

Survey of Ophthalmology, 2008

Until recently, the evidence that lowering intraocular pressure (IOP) protects the optic nerve fr... more Until recently, the evidence that lowering intraocular pressure (IOP) protects the optic nerve from glaucomatous damage was weak. Several randomized controlled trials have provided stronger evidence that lowering IOP prevents glaucomatous progression. Optic nerves appear to be highly variable in their susceptibility to raised IOP. Elevated IOP likely triggers several parallel, but interacting mechanisms, including direct axonal damage, failure of load-bearing tissues, and disturbances in microvascular supply. The cellular mechanisms that translate these mechanical and physiologic stresses and that lead to excavation of optic nerve tissue are beginning to be understood.

Ophthalmology, 1997

The purpose of the study is to determine the comparability of the 30-2 full-threshold program in ... more The purpose of the study is to determine the comparability of the 30-2 full-threshold program in the original Humphrey Field Analyzer (HFA) I to the same test procedure in the new Humphrey Field Analyzer II. At each of five clinical centers, one eye of patients with ocular hypertension and normal visual fields, patients with early glaucomatous visual field loss, and patients with more advanced visual field loss were tested with the two instruments plus a retest on a separate HFA I. All participants had undergone at least one prior visual field examination. To minimize the influence of any residual learning or fatigue effects, the order of testing for the three visual field examinations was counterbalanced across subjects. A total of 250 patients were tested (81 patients with ocular hypertension, 81 patients with early glaucomatous visual field loss, and 88 patients with more advanced glaucomatous visual field loss). No statistically significant differences were observed between thresholds, visual field indices, or reliability indices obtained with the HFA I and the HFA II. The small differences between the two instruments were equivalent to the variation observed for test-retest measures using only the HFA I. These results were consistent across the range of visual field characteristics shown by the ocular hypertensive, early glaucoma, and moderate glaucoma patient groups. The authors' results indicate that there are no differences in the visual field results obtained with the HFA I and the HFA II. These findings suggest that with careful attention to test protocols, the HFA I and HFA II may be used interchangeably to observe patients, even within the context of multicenter clinical trials.

Survey of Ophthalmology, 1998

Vascular abnormality and altered hemodynamics play important roles in many ophthalmic pathologies... more Vascular abnormality and altered hemodynamics play important roles in many ophthalmic pathologies. Much of our knowledge of ocular hemodynamics was gained from invasive animal research, although a number of noninvasive methods suitable for in vivo use in humans have been developed. Data from these methods now produce a significant literature of their own. Understanding the origins of the data and appreciating their limitations can be difficult. Modern hemodynamic assessment techniques each examine a unique facet of the ocular circulation. No single facet provides a complete description of the hemodynamic state of the eye. These methods have contributed a great deal to our understanding of normal hemodynamics. More importantly, they continue to add to our understanding of altered hemodynamics found in disease. Some have found their way into limited clinical practice. The predominant ocular hemodynamic assessment techniques are reviewed with the aims of introducing the fundamental principles behind each, highlighting their inherent advantages and limitations, highlighting their contributions to understanding ocular physiology, and considering their potential to provide signs for diagnosis.

Optometry and Vision Science, 2001

To study the spatial relationship between local functional abnormalities found using multifocal e... more To study the spatial relationship between local functional abnormalities found using multifocal electroretinography (MERG) and those measured using standard automated perimetry (SAP) in a group of glaucoma patients with well-defined, localized visual field loss. MERG's were measured for 15 patients with longstanding, stable, localized SAP visual field loss and for 27 normal controls using VERIS Science (EDI, San Mateo, CA). Most glaucoma patients had substantial asymmetry of visual field defects across the horizontal midline so that within-eye comparisons of MERG changes could be made in addition to comparisons between glaucoma and healthy, aged-matched controls. For the glaucoma patient group as a whole, conventional measurements of MERG responses, such as peak-to-trough amplitude, peak implicit time, and scalar-product density, did not reveal abnormalities that spatially corresponded to local sensitivity losses determined by SAP visual field thresholds. Some of the patients had MERG abnormalities (e.g., reduced amplitudes) in areas of advanced SAP visual field loss that indicated local retinal dysfunction. On average, glaucoma patients were missing a MERG component that resembled the optic nerve head component as described by Sutter and Bearse. Different MERG components may be affected at different stages of glaucoma, perhaps reflecting a diversity of pathophysiologic mechanisms. This may complicate spatial and temporal relationships between abnormalities found using the MERG and behavioral perimetry, particularly when conventional measurements of MERG responses are used to characterize a diverse patient group/disease.

Journal of the Optical Society of America A, 1995

Foveal sensitivities were measured after onset of adapting background fields for each of the foll... more Foveal sensitivities were measured after onset of adapting background fields for each of the following four groups of subjects aged 40-70 years: (1) low-tension glaucoma subjects with minimal field loss in the test eye, (2) primary open-angle glaucoma subjects with minimal field loss in the test eye, (3) normal control subjects, and (4) subjects originally enrolled as control subjects but subsequently found, on the basis of masked clinical evaluation, to be suspect for glaucoma despite ostensibly normal intraocular pressures. We found that the desensitization of a short-wavelength-sensitive-cone-mediated response after onset of a 580-nm background field was diminished from that of normal observers for low-tension glaucoma subjects but not for primary open-angle glaucoma subjects. The desensitization was also diminished for a glaucoma-suspect subjects aged 60-70 years. In contrast, the flicker sensitivity instabilities that persisted after onset of a long-wavelength background field for the majority of subjects with primary open-angle glaucoma [J. Glaucoma Suppl. 3, S19 (1994)] occurred only infrequently among the other subject groups. These results imply that glaucoma often involves the fovea, probably by affecting retinal subtractive adaptation processes, although with different consequences for different types of glaucoma. The results also suggest that undiagnosed low-tension glaucoma may not be rare in the general aging population.

Ophthalmology, 2010

To evaluate the predictive ability of baseline confocal scanning laser ophthalmoscopy (CSLO) Glau... more To evaluate the predictive ability of baseline confocal scanning laser ophthalmoscopy (CSLO) Glaucoma Probability Score (GPS) for the development of primary open-angle glaucoma (POAG) and to compare it with the Moorfields regression analysis (MRA) classification, other topographic optic disc parameters, and stereophotograph-based cup-to-disc ratio. Longitudinal, randomized clinical trial. We included 857 eyes of 438 participants in the CSLO Ancillary Study to the Ocular Hypertension Treatment Study (OHTS) with good quality baseline CSLO images. The ability of baseline GPS, MRA, and optic disc parameters to predict the development of POAG was evaluated in univariate and multivariable proportional hazard ratio analyses. Likelihood ratios and positive and negative predictive values were compared. The POAG end point as determined by repeatable changes in the visual field or optic disc. Sixty-four eyes of 50 CSLO Ancillary Study participants developed POAG. Median time to reach a POAG end point was 72.3 months. The 93 eyes of 388 participants not reaching endpoint were followed for a median of 124.9 months. Baseline GPS identified many more eyes as outside normal limits than the MRA. In multivariable analyses, all regional and global baseline GPS indices were significantly associated with the development of POAG; hazard ratios (95% confidence interval) ranged from 2.92 to 3.74 for an outside normal limits result. The MRA indices were also significantly associated with the development of POAG in multivariable analyses. In addition, the predictive ability of baseline GPS, MRA and stereometric parameters were similar to the predictive ability of models using photograph-based horizontal cup-to-disc ratio. These results suggest that baseline GPS, MRA, and stereoparameters alone or when combined with baseline clinical and demographic factors can be used to predict the development of POAG end points in OHTS participants and are as effective as stereophotographs for estimating the risk of developing POAG in ocular hypertensive subjects.

Ophthalmic Epidemiology, 2007

To determine if a community screening with Frequency Doubling Technology perimetry (FDT) results ... more To determine if a community screening with Frequency Doubling Technology perimetry (FDT) results in a high proportion of follow-up with an eye care provider and the factors associated with follow-up. Cross-sectional study. Telephone survey We conducted a telephone survey of participants with abnormal results 3-6 months after the community screening. We were able to interview 121 participants (57% of 212 eligible subjects). Sixty-nine percent (83 of 121) of participants visited an eye care provider after the screening. Patients were more likely to attain an eye exam if they were female, older, or had an educational level of high school or more (p<0.05). Of those participants who did not visit an eye care provider, 41% (18/38) did not believe the results of the test, 21% (8/38) reported not having insurance or an eye care provider, 11% (4/38) did not have time for an eye exam, and 11% (4/38) reported not knowing they needed to see an eye care provider. A community screening program with FDT encouraged more than two thirds of participants with abnormal results to seek an eye exam. The most common reason not to attain an eye exam was failing to recognize the importance of an abnormal test result.

Journal of Glaucoma, 2005

To evaluate ganglion cell loss in early glaucoma using a variety of psychophysical tests and to i... more To evaluate ganglion cell loss in early glaucoma using a variety of psychophysical tests and to identify optimal perimetric technique(s) for detection of early glaucomatous visual function loss. Five perimetric tests, short wavelength automated perimetry (SWAP), temporal modulation perimetry (TMP), frequency doubling technology perimetry (FDT), detection acuity perimetry (DAP), and resolution acuity perimetry (RAP) were compared in their ability to discriminate between normal individuals and patients with early glaucoma or glaucoma suspects. Comparisons were also made by their ability to produce repeatable defects. The tests examined different visual functions that are likely to be mediated by different retinal ganglion cell subpopulations, thereby permitting examination of hypotheses of ganglion cell death in early glaucoma. All visual field tests demonstrated high performance in separating glaucoma patients from normal individuals. SWAP, TMP, FDT, and DAP provided the greatest discrimination between normal individuals and high- and low-risk glaucoma suspects. However, SWAP, TMP, and FDT obtained better consistency across the various analysis approaches (global indices and pointwise) than DAP and RAP. Of all the test types, FDT exhibited the highest proportion of repeatable abnormal test locations, with poor confirmation rates achieved by DAP and RAP. The performance of SWAP, FDT, and TMP suggests that these test types may all be suitable for detection of early loss of visual function in glaucoma. Ganglion cell subpopulations with lower levels of redundancy and/or those with larger cell sizes offer the most parsimonious explanation for earliest ganglion cell losses occurring in glaucoma.

PURPOSE. To evaluate electrophysiologic function in glaucoma by using a new stimulus designed to ... more PURPOSE. To evaluate electrophysiologic function in glaucoma by using a new stimulus designed to enhance ganglion cell and optic nerve head component (ONHC) contributions to multi- focal electroretinogram (mfERG) responses. METHODS. mfERGs of 16 individuals with glaucoma (POAG) and 18 normal control subjects were recorded and analyzed with a VER imaging system. The stimulus had three frames inserted between each

Optometry and Vision Science, 1999

To assess whether smaller targets and a 24-2 stimulus presentation pattern would improve the abil... more To assess whether smaller targets and a 24-2 stimulus presentation pattern would improve the ability of frequency doubling technology (FDT) perimetry to detect and characterize early glaucomatous visual field loss. One hundred normal subjects between the ages of 20 and 85 participated in this study. In addition, 53 patients who either had early glaucomatous visual field loss (n = 23) or were high-risk glaucoma suspects with normal conventional visual fields (n = 30) were evaluated with the commercial version of FDT perimetry (full threshold test) with 17 stimuli (four 10 degrees diameter square targets per quadrant and a central 5 degrees circular target) and a custom version of FDT perimetry using 54 stimuli (4 degrees targets with 6 degrees grid spacing) arranged in a 24-2 stimulus presentation pattern. The custom FDT test using a 24-2 stimulus presentation pattern had a similar dynamic range, and demonstrated normal aging characteristics and test-retest reliability that were similar to the commercial version of FDT perimetry using 17 larger stimuli. Both FDT tests showed an age-related sensitivity reduction of approximately 0.6 dB per decade, and exhibited an average test-retest reliability of 1 to 1.5 dB. The custom 24-2 FDT perimetry test had a greater variation of sensitivity with eccentricity than the commercial version of FDT perimetry that was probably related to the difference in stimulus size. The custom 24-2 FDT perimetry test had a greater percentage of abnormal test locations than the commercial FDT test for both early glaucomas and high-risk glaucoma suspects. FDT perimetry can be performed with smaller targets using a presentation pattern that is similar to conventional automated perimetry. In comparison to the commercially available 17 target display, the 24-2 stimulus pattern appears to have modestly higher sensitivity for detection of early glaucomatous loss and provides better characterization of the pattern of visual field loss, but the test takes approximately twice as long.

Journal of Neuro-ophthalmology, 1996

Methyl methacrylate vascular corrosion casting techniques were used to examine the normal anterio... more Methyl methacrylate vascular corrosion casting techniques were used to examine the normal anterior optic nerve microvasculature in 18 human eye bank eyes. Selective cannulation of the central retinal artery, the short posterior ciliary arteries, or both, allowed the methyl methacrylate to be injected into the anterior optic nerve circulation. Preflushing with tissue plasminogen activator greatly enhanced the filling of the fine microvasculature by dissolving the intraluminal clots. The superficial nerve fiber layer of the optic nerve received its primary blood supply from the central retinal artery. In 11 of 13 eyes injected with methyl methacrylate through the short posterior ciliary arteries, there was a perineural, circular arterial anastomosis (circle of Zinn-Haller) at the scleral level. Branches from this circle penetrated the optic nerve to supply the prelaminar and laminar regions and the peripapillary choroid. In the two eyes without this arterial circle, direct branches from the short posterior ciliary arteries supplied the anterior optic nerve. The venous drainage of the anterior optic nerve was almost entirely through the central retinal vein and its tributaries. This study demonstrates that the main arterial vascular supply to the anterior optic nerve is from the short posterior ciliary arteries. The contribution of the peripapillary choroid to the anterior optic nerve is minimal in comparison to the direct contribution from the short posterior ciliary arteries.

JAMA Ophthalmology, 2015

Understanding factors that lead to nonadherence to glaucoma treatment is important to diminish gl... more Understanding factors that lead to nonadherence to glaucoma treatment is important to diminish glaucoma-related disability. To determine whether the implementation of the Medicare Part D prescription drug benefit affected rates of cost-related nonadherence and cost-reduction strategies in Medicare beneficiaries with and without glaucoma and to evaluate associated risk factors for such nonadherence. Serial cross-sectional study using 2004 to 2009 Medicare Current Beneficiary Survey data linked with Medicare claims. Coding to extract data started in January 2014 and analyses were performed between September and November of 2014. Participants were all Medicare beneficiaries, including those with a glaucoma-related diagnosis in the year prior to the collection of the survey data, those with a nonglaucomatous ophthalmic diagnosis in the year prior to the collection of the survey data, and those without a recent eye care professional claim. Effect of the implementation of the Medicare Part D drug benefit. The change in cost-related nonadherence and the change in cost-reduction strategies. Between 2004 and 2009, the number of Medicare beneficiaries with glaucoma who reported taking smaller doses and skipping doses owing to cost dropped from 9.4% and 8.2% to 2.7% (P < .001) and 2.8%, respectively (P = .001). However, reports of failure to obtain prescriptions owing to cost did not improve in the same period (3.4% in 2004 and 2.1% in 2009; P = .12). After Part D, patients with glaucoma had a decrease in several cost-reduction strategies, namely price shopping (26.2%-15.2%; P < .001), purchasing outside the United States (6.9%-1.3%; P < .001), and spending less money to save for medications (8.0% to 3.5%; P < .001). Using a multivariate analysis, the main independent risk factors common to all cost-related nonadherence measures were female sex, younger age, lower income (<$30 000), self-reported visual disability, and a smaller Lawton index. After the implementation of Part D, there was a decrease in the rate that beneficiaries with glaucoma reported engaging in cost-saving measures. Although there was a decline in the rate of several cost-related nonadherence behaviors, patients reporting failure to fill prescriptions owing to cost remained stable. This suggests that efforts to improve cost-related nonadherence should focus both on financial hardship and medical therapy prioritization, particularly in certain high-risk sociodemographic groups.

Seminars in ophthalmology, 2000

This article reviews the relationships between structural changes and visual function losses prod... more This article reviews the relationships between structural changes and visual function losses produced by glaucomatous damage. Structural characteristics of the optic nerve head and retinal nerve fiber layer include both qualitative and semi-quantitative clinical assessment methods as well as quantitative imaging techniques. Visual function properties include standard (white-on-white) automated perimetry and new techniques such as short wavelength automated perimetry and motion displacement threshold perimetry. Previous investigations consistently report a significant relationship between structural and functional deficits in glaucoma, with structural changes usually being reported to occur earlier than functional losses. In cases of focal damage, there appears to be a good topographic relationship between structural and functional losses. Several optic nerve head and retinal nerve fiber layer measures are reported to be good predictors of glaucomatous visual field loss. However, pre...

Archives of ophthalmology, 2005

To determine whether baseline confocal scanning laser ophthalmoscopy (CSLO) optic disc topographi... more To determine whether baseline confocal scanning laser ophthalmoscopy (CSLO) optic disc topographic measurements are associated with the development of primary open-angle glaucoma (POAG) in individuals with ocular hypertension. Eight hundred sixty-five eyes from 438 participants in the CSLO Ancillary Study to the Ocular Hypertension Treatment Study with good-quality baseline CSLO images were included in this study. Each baseline CSLO parameter was assessed in univariate and multivariate proportional hazards models to determine its association with the development of POAG. Forty-one eyes from 36 CSLO Ancillary Study participants developed POAG. Several baseline topographic optic disc measurements were significantly associated with the development of POAG in both univariate and multivariate analyses, including larger cup-disc area ratio, mean cup depth, mean height contour, cup volume, reference plane height, and smaller rim area, rim area to disc area, and rim volume. In addition, cla...

Documenta ophthalmologica. Advances in ophthalmology, 2002

While elevated intraocular pressure (IOP) undoubtedly plays a crucial role in many glaucoma patie... more While elevated intraocular pressure (IOP) undoubtedly plays a crucial role in many glaucoma patients, vascular dysregulation and chronic regional ischemia are also thought to contribute to the pathophysiology of glaucoma. In an effort to critically evaluate hypotheses involving vascular abnormalities in glaucoma, Cioffi, Van Buskirk and co-workers have developed a model of optic neuropathy based on chronic regional ischemia. The multifocal electroretinogram (MERG) has previously been used to assess function in non-human primates with experimental glaucoma induced by high-IOP. In this study, the MERG was used to monitor function in macaque monkeys with experimental glaucoma induced by chronic anterior optic nerve ischemia. Initial recordings from experimental eyes, which were later documented histologically to have moderate axon loss, revealed little difference from recordings of control eyes. This suggested that many of the signal components in the macaque MERG, which are known (fro...

Investigative ophthalmology & visual science, 2002

Glial cells are structurally and functionally linked to neuronal tissues. Pathologically, the cel... more Glial cells are structurally and functionally linked to neuronal tissues. Pathologically, the cells may be activated and characterized by increased size and number and altered cellular properties. In glaucoma, pathologic mechanisms within the anterior optic nerve may include glial activation. This study examines morphologic changes of glial cells in the retinas of glaucomatous eyes compared with age-matched control retinas. Paraffin-processed or flatmounted retinas from 17 human donor eyes [7 normal (donor age, 87.3 +/- 8.3 years) and 10 glaucomatous (donor age, 87.1 +/- 6.9 years)] were examined. With immunohistochemical methods, retinal glial cells were stained with an antibody to glial fibrillary acidic protein (GFAP). The morphology of the glial cells in normal and glaucomatous retinas was evaluated with fluorescence microscopy. Three types of glial cells were identified in flatmounted retinas with differing distributions in the peripapillary region, the nerve fiber layer (NFL),...

Archives of ophthalmology, 1998

To develop a brief symptom survey specific for persons with glaucoma, the Glaucoma Symptom Scale ... more To develop a brief symptom survey specific for persons with glaucoma, the Glaucoma Symptom Scale (GSS). Cross-sectional study of symptoms, functional impairment, and vision-targeted health-related quality of life among persons with glaucoma. A sample of 147 persons with glaucoma among a broad range of treatment categories from 4 tertiary care glaucoma centers and 44 persons without eye disease enrolled from the same 4 centers. Participants completed a modified version of the Ocular Hypertension Treatment Study 10-item symptom checklist. Participants also completed 2 vision-specific measures, the National Eye Institute Visual Function Questionnaire and the VF-14. Participants underwent a clinical evaluation, including ocular and medical history, dilated ophthalmic examination, and Humphrey 24-2 automated visual field testing. The GSS has 2 underlying domains that demonstrate sufficient internal consistency reliability for between-group comparisons. The GSS discriminates well between ...

Translational Vision Science & Technology, 2015

Citation: Susanna Jr R, De Moraes CG, Cioffi GA, Ritch R. Why do people (still) go blind from gla... more Citation: Susanna Jr R, De Moraes CG, Cioffi GA, Ritch R. Why do people (still) go blind from glaucoma? Trans Vis Sci Tech. 2015;4(1): 10, http://tvstjournal.org/doi/full/

JAMA ophthalmology, Jan 5, 2015

The Tube vs Trabeculectomy Trial (TVT) found that the 350-mm2 Baerveldt implant (tube) and trabec... more The Tube vs Trabeculectomy Trial (TVT) found that the 350-mm2 Baerveldt implant (tube) and trabeculectomy with mitomycin may be similarly effective in lowering intraocular pressure in primary open-angle glaucoma. However, to date, there are no published long-term clinical data on the cost-effectiveness of trabeculectomy with mitomycin vs tube insertion. To assess the cost-effectiveness of these procedures compared with maximal medical treatment. We used the Markov cohort model with a 5-year time horizon to study a hypothetical cohort of 100 000 patients who required glaucoma surgery. Quality-adjusted life-years (QALYs) gained, costs from the societal perspective, and the incremental cost-effectiveness ratio of medical treatment, trabeculectomy, and tube insertion. Costs were identified from Medicare Current Procedural Terminology and Ambulatory Payment Classification reimbursement codes and Red Book medication costs. The QALYs were based on visual field and visual acuity outcomes. T...

Survey of Ophthalmology, 2008

Until recently, the evidence that lowering intraocular pressure (IOP) protects the optic nerve fr... more Until recently, the evidence that lowering intraocular pressure (IOP) protects the optic nerve from glaucomatous damage was weak. Several randomized controlled trials have provided stronger evidence that lowering IOP prevents glaucomatous progression. Optic nerves appear to be highly variable in their susceptibility to raised IOP. Elevated IOP likely triggers several parallel, but interacting mechanisms, including direct axonal damage, failure of load-bearing tissues, and disturbances in microvascular supply. The cellular mechanisms that translate these mechanical and physiologic stresses and that lead to excavation of optic nerve tissue are beginning to be understood.

Ophthalmology, 1997

The purpose of the study is to determine the comparability of the 30-2 full-threshold program in ... more The purpose of the study is to determine the comparability of the 30-2 full-threshold program in the original Humphrey Field Analyzer (HFA) I to the same test procedure in the new Humphrey Field Analyzer II. At each of five clinical centers, one eye of patients with ocular hypertension and normal visual fields, patients with early glaucomatous visual field loss, and patients with more advanced visual field loss were tested with the two instruments plus a retest on a separate HFA I. All participants had undergone at least one prior visual field examination. To minimize the influence of any residual learning or fatigue effects, the order of testing for the three visual field examinations was counterbalanced across subjects. A total of 250 patients were tested (81 patients with ocular hypertension, 81 patients with early glaucomatous visual field loss, and 88 patients with more advanced glaucomatous visual field loss). No statistically significant differences were observed between thresholds, visual field indices, or reliability indices obtained with the HFA I and the HFA II. The small differences between the two instruments were equivalent to the variation observed for test-retest measures using only the HFA I. These results were consistent across the range of visual field characteristics shown by the ocular hypertensive, early glaucoma, and moderate glaucoma patient groups. The authors' results indicate that there are no differences in the visual field results obtained with the HFA I and the HFA II. These findings suggest that with careful attention to test protocols, the HFA I and HFA II may be used interchangeably to observe patients, even within the context of multicenter clinical trials.

Survey of Ophthalmology, 1998

Vascular abnormality and altered hemodynamics play important roles in many ophthalmic pathologies... more Vascular abnormality and altered hemodynamics play important roles in many ophthalmic pathologies. Much of our knowledge of ocular hemodynamics was gained from invasive animal research, although a number of noninvasive methods suitable for in vivo use in humans have been developed. Data from these methods now produce a significant literature of their own. Understanding the origins of the data and appreciating their limitations can be difficult. Modern hemodynamic assessment techniques each examine a unique facet of the ocular circulation. No single facet provides a complete description of the hemodynamic state of the eye. These methods have contributed a great deal to our understanding of normal hemodynamics. More importantly, they continue to add to our understanding of altered hemodynamics found in disease. Some have found their way into limited clinical practice. The predominant ocular hemodynamic assessment techniques are reviewed with the aims of introducing the fundamental principles behind each, highlighting their inherent advantages and limitations, highlighting their contributions to understanding ocular physiology, and considering their potential to provide signs for diagnosis.

Optometry and Vision Science, 2001

To study the spatial relationship between local functional abnormalities found using multifocal e... more To study the spatial relationship between local functional abnormalities found using multifocal electroretinography (MERG) and those measured using standard automated perimetry (SAP) in a group of glaucoma patients with well-defined, localized visual field loss. MERG's were measured for 15 patients with longstanding, stable, localized SAP visual field loss and for 27 normal controls using VERIS Science (EDI, San Mateo, CA). Most glaucoma patients had substantial asymmetry of visual field defects across the horizontal midline so that within-eye comparisons of MERG changes could be made in addition to comparisons between glaucoma and healthy, aged-matched controls. For the glaucoma patient group as a whole, conventional measurements of MERG responses, such as peak-to-trough amplitude, peak implicit time, and scalar-product density, did not reveal abnormalities that spatially corresponded to local sensitivity losses determined by SAP visual field thresholds. Some of the patients had MERG abnormalities (e.g., reduced amplitudes) in areas of advanced SAP visual field loss that indicated local retinal dysfunction. On average, glaucoma patients were missing a MERG component that resembled the optic nerve head component as described by Sutter and Bearse. Different MERG components may be affected at different stages of glaucoma, perhaps reflecting a diversity of pathophysiologic mechanisms. This may complicate spatial and temporal relationships between abnormalities found using the MERG and behavioral perimetry, particularly when conventional measurements of MERG responses are used to characterize a diverse patient group/disease.

Journal of the Optical Society of America A, 1995

Foveal sensitivities were measured after onset of adapting background fields for each of the foll... more Foveal sensitivities were measured after onset of adapting background fields for each of the following four groups of subjects aged 40-70 years: (1) low-tension glaucoma subjects with minimal field loss in the test eye, (2) primary open-angle glaucoma subjects with minimal field loss in the test eye, (3) normal control subjects, and (4) subjects originally enrolled as control subjects but subsequently found, on the basis of masked clinical evaluation, to be suspect for glaucoma despite ostensibly normal intraocular pressures. We found that the desensitization of a short-wavelength-sensitive-cone-mediated response after onset of a 580-nm background field was diminished from that of normal observers for low-tension glaucoma subjects but not for primary open-angle glaucoma subjects. The desensitization was also diminished for a glaucoma-suspect subjects aged 60-70 years. In contrast, the flicker sensitivity instabilities that persisted after onset of a long-wavelength background field for the majority of subjects with primary open-angle glaucoma [J. Glaucoma Suppl. 3, S19 (1994)] occurred only infrequently among the other subject groups. These results imply that glaucoma often involves the fovea, probably by affecting retinal subtractive adaptation processes, although with different consequences for different types of glaucoma. The results also suggest that undiagnosed low-tension glaucoma may not be rare in the general aging population.

Ophthalmology, 2010

To evaluate the predictive ability of baseline confocal scanning laser ophthalmoscopy (CSLO) Glau... more To evaluate the predictive ability of baseline confocal scanning laser ophthalmoscopy (CSLO) Glaucoma Probability Score (GPS) for the development of primary open-angle glaucoma (POAG) and to compare it with the Moorfields regression analysis (MRA) classification, other topographic optic disc parameters, and stereophotograph-based cup-to-disc ratio. Longitudinal, randomized clinical trial. We included 857 eyes of 438 participants in the CSLO Ancillary Study to the Ocular Hypertension Treatment Study (OHTS) with good quality baseline CSLO images. The ability of baseline GPS, MRA, and optic disc parameters to predict the development of POAG was evaluated in univariate and multivariable proportional hazard ratio analyses. Likelihood ratios and positive and negative predictive values were compared. The POAG end point as determined by repeatable changes in the visual field or optic disc. Sixty-four eyes of 50 CSLO Ancillary Study participants developed POAG. Median time to reach a POAG end point was 72.3 months. The 93 eyes of 388 participants not reaching endpoint were followed for a median of 124.9 months. Baseline GPS identified many more eyes as outside normal limits than the MRA. In multivariable analyses, all regional and global baseline GPS indices were significantly associated with the development of POAG; hazard ratios (95% confidence interval) ranged from 2.92 to 3.74 for an outside normal limits result. The MRA indices were also significantly associated with the development of POAG in multivariable analyses. In addition, the predictive ability of baseline GPS, MRA and stereometric parameters were similar to the predictive ability of models using photograph-based horizontal cup-to-disc ratio. These results suggest that baseline GPS, MRA, and stereoparameters alone or when combined with baseline clinical and demographic factors can be used to predict the development of POAG end points in OHTS participants and are as effective as stereophotographs for estimating the risk of developing POAG in ocular hypertensive subjects.

Ophthalmic Epidemiology, 2007

To determine if a community screening with Frequency Doubling Technology perimetry (FDT) results ... more To determine if a community screening with Frequency Doubling Technology perimetry (FDT) results in a high proportion of follow-up with an eye care provider and the factors associated with follow-up. Cross-sectional study. Telephone survey We conducted a telephone survey of participants with abnormal results 3-6 months after the community screening. We were able to interview 121 participants (57% of 212 eligible subjects). Sixty-nine percent (83 of 121) of participants visited an eye care provider after the screening. Patients were more likely to attain an eye exam if they were female, older, or had an educational level of high school or more (p<0.05). Of those participants who did not visit an eye care provider, 41% (18/38) did not believe the results of the test, 21% (8/38) reported not having insurance or an eye care provider, 11% (4/38) did not have time for an eye exam, and 11% (4/38) reported not knowing they needed to see an eye care provider. A community screening program with FDT encouraged more than two thirds of participants with abnormal results to seek an eye exam. The most common reason not to attain an eye exam was failing to recognize the importance of an abnormal test result.

Journal of Glaucoma, 2005

To evaluate ganglion cell loss in early glaucoma using a variety of psychophysical tests and to i... more To evaluate ganglion cell loss in early glaucoma using a variety of psychophysical tests and to identify optimal perimetric technique(s) for detection of early glaucomatous visual function loss. Five perimetric tests, short wavelength automated perimetry (SWAP), temporal modulation perimetry (TMP), frequency doubling technology perimetry (FDT), detection acuity perimetry (DAP), and resolution acuity perimetry (RAP) were compared in their ability to discriminate between normal individuals and patients with early glaucoma or glaucoma suspects. Comparisons were also made by their ability to produce repeatable defects. The tests examined different visual functions that are likely to be mediated by different retinal ganglion cell subpopulations, thereby permitting examination of hypotheses of ganglion cell death in early glaucoma. All visual field tests demonstrated high performance in separating glaucoma patients from normal individuals. SWAP, TMP, FDT, and DAP provided the greatest discrimination between normal individuals and high- and low-risk glaucoma suspects. However, SWAP, TMP, and FDT obtained better consistency across the various analysis approaches (global indices and pointwise) than DAP and RAP. Of all the test types, FDT exhibited the highest proportion of repeatable abnormal test locations, with poor confirmation rates achieved by DAP and RAP. The performance of SWAP, FDT, and TMP suggests that these test types may all be suitable for detection of early loss of visual function in glaucoma. Ganglion cell subpopulations with lower levels of redundancy and/or those with larger cell sizes offer the most parsimonious explanation for earliest ganglion cell losses occurring in glaucoma.