Robert T. Chang

Macular Ganglion Cell–Inner Plexiform Layer: Automated Detection and Thickness Reproducibility with Spectral Domain–Optical Coherence Tomography in Glaucoma

PURPOSE To demonstrate the capability of SD-OCT to measure macular retinal ganglion cell-inner plexiform layer (GCIPL) thickness and to assess its reproducibility in glaucomatous eyes. METHODS Fifty-one glaucomatous eyes (26 mild, 11 moderate, 14 severe) of 51 patients underwent macular scanning using the Cirrus HD-OCT (Carl Zeiss Meditec, Dublin, CA) macula 200×200 acquisition protocol. Five scans were obtained on 5 days within 2 months. The ganglion cell analysis (GCA) algorithm was used to detect the macular GCIPL and to measure the thickness of the overall average, minimum, superotemporal, superior, superonasal, inferonasal, inferior, and inferotemporal GCIPL. The reproducibility of the measurements was evaluated with intraclass correlation coefficients (ICCs), coefficients of variation (COVs), and test-retest standard deviations (TRTSDs). RESULTS Segmentation and measurement of GCIPL thickness were successful in 50 of 51 subjects. All ICCs ranged between 0.94 and 0.98, but ICCs for average and superior GCIPL parameters (0.97-0.98) were slightly higher than for inferior GCIPL parameters (0.94-0.97). All COVs were <5%, with 1.8% for average GCIPL and COVs for superior GCIPL parameters (2.2%-3.0%) slightly lower than those for inferior GCIPL parameters (2.5%-3.6%). The TRTSD was lowest for average GCIPL (1.16 μm) and varied from 1.43 to 2.15 μm for sectoral GCIPL CONCLUSIONS: The Cirrus HD-OCT GCA algorithm can successfully segment macular GCIPL and measure GCIPL thickness with excellent intervisit reproducibility. Longitudinal monitoring of GCIPL thickness may be possible with Cirrus HD-OCT for assessing glaucoma progression.

Glaucoma Diagnostic Accuracy of Ganglion Cell–Inner Plexiform Layer Thickness: Comparison with Nerve Fiber Layer and Optic Nerve Head

PURPOSE To determine the diagnostic performance of macular ganglion cell-inner plexiform layer (GCIPL) thickness measured with the Cirrus high-definition optical coherence tomography (HD-OCT) ganglion cell analysis (GCA) algorithm (Carl Zeiss Meditec, Dublin, CA) to discriminate normal eyes and eyes with early glaucoma and to compare it with that of peripapillary retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) measurements. DESIGN Evaluation of diagnostic test or technology. PARTICIPANTS Fifty-eight patients with early glaucoma and 99 age-matched normal subjects. METHODS Macular GCIPL and peripapillary RNFL thicknesses and ONH parameters were measured in each participant, and their diagnostic abilities were compared. MAIN OUTCOME MEASURES Area under the curve (AUC) of the receiver operating characteristic. RESULTS The GCIPL parameters with the best AUCs were the minimum (0.959), inferotemporal (0.956), average (0.935), superotemporal (0.919), and inferior sector (0.918). There were no significant differences between these AUCs and those of inferior quadrant (0.939), average (0.936), and superior quadrant RNFL (0.933); vertical cup-to-disc diameter ratio (0.962); cup-to-disc area ratio (0.933); and rim area (0.910), all P>0.05. CONCLUSIONS The ability of macular GCIPL parameters to discriminate normal eyes and eyes with early glaucoma is high and comparable to that of the best peripapillary RNFL and ONH parameters. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Comparison of Retinal Nerve Fiber Layer Measurements Using Time Domain and Spectral Domain Optical Coherent Tomography

PURPOSE To determine the agreement between peripapillary retinal nerve fiber layer (RNFL) thickness measurements from Stratus time domain optical coherence tomography (OCT) and Cirrus spectral domain OCT (Carl Zeiss Meditec, Dublin, CA) in normal subjects and subjects with glaucoma. DESIGN Evaluation of diagnostic test or technology. PARTICIPANTS A total of 130 eyes from 130 normal subjects and subjects with glaucoma were analyzed. The subjects were divided into groups by visual field criteria: normal (n = 29), glaucoma suspect (n = 12), mild glaucoma (n = 41), moderate glaucoma (n = 18), and severe glaucoma (n = 30). METHODS Peripapillary RNFL thickness was measured with Stratus Fast RNFL and Cirrus 200 x 200 Optic Disc Scan on the same day in 1 eye of each subject to determine agreement. Two operators used the same instruments for all scans. MAIN OUTCOME MEASURES Student paired t testing, Pearsons correlation coefficient, and Bland-Altman analysis of RNFL thickness measurements. RESULTS The average age of the glaucoma group was significantly more than that of the normal group: 68.3+/-12.3 years versus 55.7+/-12.1 years, respectively. For Stratus OCT, the average RNFL thickness (mean +/- standard deviation) was 99.4+/-13.2 microm, 94.5+/-15.0 microm, 79.0+/-14.5 microm, 62.7+/-10.2 microm, and 51.0+/-8.9 microm for the normal, suspect, mild, moderate, and severe groups, respectively. For Cirrus OCT, the corresponding measurements were 92.0+/-10.8 microm, 88.1+/-13.5 microm, 73.3+/-11.8 microm, 60.9+/-8.3 microm, and 55.3+/-6.6 microm. All Stratus-Cirrus differences were statistically significant by paired t testing (P<0.001) except for the moderate group (P = 0.11). For average RNFL, there was also a highly significant linear relationship between Stratus minus Cirrus difference and RNFL thickness (P<0.001). Bland-Altman plots showed that the systematic difference of Stratus measurements are smaller than Cirrus at thinner RNFL values but larger at thicker RNFL values. CONCLUSIONS RNFL thickness measurements between Stratus OCT and Cirrus OCT cannot be directly compared. Clinicians should be aware that measurements are generally higher with Stratus than with Cirrus except when the RNFL is very thin, as in severe glaucoma. This difference must be taken into account if comparing Stratus measurements with Cirrus measurements.

Reproducibility of peripapillary retinal nerve fiber layer thickness and optic nerve head parameters measured with cirrus HD-OCT in glaucomatous eyes.

PURPOSE To assess the reproducibility of peripapillary retinal nerve fiber layer (RNFL) thickness and optic nerve head (ONH) parameters measured with Cirrus HD-OCT in glaucomatous eyes. METHODS Fifty-five glaucomatous eyes were included in the study. The optic disc cube 200 × 200 protocol was used to obtain three scans during the same visit to evaluate the intravisit reproducibility. One scan on 4 additional days within a 2-month period of the first session was obtained to assess intervisit reproducibility. Intraclass correlation coefficient (ICC), coefficient of variation (CV), and test-retest SD (TRT SD) were calculated for each RNFL and ONH parameter. The formula 1.645 × √2 × intervisit TRT SD provides an upper tolerance limit to variability beyond which nonphysiologic change should be considered. RESULTS All ICCs were excellent, ranging from 83.9% to 99.2% for intravisit measurements and from 80.8% to 99.1% for intervisit measurements. Cup/disc area ratio had the lowest CV (1.1%) in either type of measurement, followed by average RNFL thickness (1.9% and 2.7%). Nasal clock hours and quadrants showed the poorest reproducibility as did the clock hour directly temporally. The intervisit tolerance limit for average RNFL thickness was 3.89 μm. CONCLUSIONS Intravisit and intervisit measurements of peripapillary RNFL thickness and ONH parameters with Cirrus HD-OCT showed excellent reproducibility, indicating that this instrument may be useful in monitoring glaucoma progression. When comparing two measurements from the same eye on two different visits, a reproducible decrease in average RNFL thickness of approximately 4 μm or more may be considered a statistically significant change from baseline.

Sensitivity and Specificity of Time-Domain versus Spectral-Domain Optical Coherence Tomography in Diagnosing Early to Moderate Glaucoma

PURPOSE To evaluate the sensitivity and specificity of measurements of retinal nerve fiber layer (RNFL) thickness in early to moderate glaucoma using Stratus time-domain and Cirrus spectral-domain optical coherence tomography (OCT; Carl Zeiss Meditec, Dublin, CA). DESIGN Evaluation of diagnostic test or technology. PARTICIPANTS Fifty-four glaucoma subjects with early to moderate visual field defects and 50 age-matched normal subjects. TESTING Three peripapillary RNFL scans of 1 eye of each subject using Stratus and Cirrus OCT. MAIN OUTCOME MEASURES Sensitivity and specificity of average, quadrant, and clock-hour RNFL thickness. RESULTS The average age+/-standard deviation in the normal and glaucoma groups was 62.9+/-12.7 years (range, 40-84 years) and 67.6+/-11.4 (range, 42-85 years), respectively (P = 0.05). The glaucoma group consisted of 34 early (average mean deviation, -3.20+/-1.22 dB) and 20 moderate (average mean deviation, -8.05+/-1.87 dB) glaucomas. Cirrus OCT sensitivity and specificity for average RNFL abnormal at the 5% level were 83% and 88%, respectively, and at the 1% level were 65% and 100%, respectively. Stratus OCT sensitivity and specificity for average RNFL abnormal at the 5% level were 80% and 94%, respectively, and at the 1% level were 61% and 100%, respectively. For 1 or more abnormal quadrants at the 5% level, the sensitivity and specificity for Cirrus OCT were 98% and 80%, respectively, and at the 1% level were 87% and 92%, respectively. For 1 or more quadrants abnormal at the 5% level, the sensitivity and specificity for Stratus OCT were 96% and 76%, respectively, and at the 1% level were 74% and 94%, respectively. Cirrus OCT sensitivity and specificity using a criterion of 1 or more abnormal clock hours at the 5% level were 100% and 72%, respectively, and at the 1% level were 85% and 94%, respectively. Stratus OCT sensitivity and specificity for 1 or more abnormal clock hours at the 5% level were 98% and 66%, respectively, and at the 1% level were 85% and 90%, respectively. CONCLUSIONS The sensitivity and specificity of various RNFL parameters using the Cirrus OCT for glaucoma with early to moderate visual field defects are excellent and are equivalent to Stratus OCT.

Antibiotic resistance patterns of ocular bacterial flora: A prospective study of patients undergoing anterior segment surgery

PURPOSE To determine the antibiotic susceptibility patterns of conjunctival bacterial flora isolated preoperatively from patients undergoing anterior segment surgery. DESIGN Prospective observational study. PARTICIPANTS One hundred fifty-six eyes from 139 patients scheduled for anterior segment surgery were enrolled over a 6-month period from August 2001 to February 2002. METHODS Conjunctival cultures were obtained on the day of surgery before povidone-iodine or antibiotic application. MAIN OUTCOME MEASURES Bacterial isolates were identified and tested for antibiotic susceptibility using the Kirby-Bauer disc-diffusion technique. RESULTS Among the 156 eyes studied, 36 were from patients who had undergone either bilateral surgery or more than one surgery in the same eye. Only the first eyes of the 120 patients that underwent initial ocular surgery were included in our analysis. Of these 120 eyes, 21 (18%) showed no bacterial growth. Of the 143 bacterial strains isolated from the remaining 99 eyes, 112 (78%) were coagulase-negative staphylococci (CNS). Among the CNS, greater than 90% were susceptible to cefotaxime, levofloxacin, imipenem, meropenem, vancomycin, and each of the aminoglycosides except neomycin. Between 70% and 90% of the CNS were susceptible to cefazolin, neomycin, ciprofloxacin, ofloxacin, norfloxacin, and chloramphenicol. Less than 70% of the isolated CNS were sensitive to the penicillin analogues, ceftazidime, erythromycin, and tetracycline. CONCLUSIONS Preoperative conjunctival isolates of CNS seem to be most sensitive to vancomycin, the aminoglycosides (except neomycin), and levofloxacin.

Diagnostic performance of optical coherence tomography ganglion cell-inner plexiform layer thickness measurements in early glaucoma

PURPOSE To evaluate the glaucoma diagnostic performance of ganglion cell inner-plexiform layer (GCIPL) parameters used individually and in combination with retinal nerve fiber layer (RNFL) or optic nerve head (ONH) parameters measured with Cirrus HD-OCT (Carl Zeiss Meditec, Inc, Dublin, CA). DESIGN Prospective cross-sectional study. PARTICIPANTS Fifty patients with early perimetric glaucoma and 49 age-matched healthy subjects. METHODS Three peripapillary RNFL and 3 macular GCIPL scans were obtained in 1 eye of each participant. A patient was considered glaucomatous if at least 2 of the 3 RNFL or GCIPL scans had the average or at least 1 sector measurement flagged at 1% to 5% or less than 1%. The diagnostic performance was determined for each GCIPL, RNFL, and ONH parameter as well as for binary or-logic and and-logic combinations of GCIPL with RNFL or ONH parameters. MAIN OUTCOME MEASURES Sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR). RESULTS Among GCIPL parameters, the minimum had the best diagnostic performance (sensitivity, 82.0%; specificity, 87.8%; PLR, 6.69; and NLR, 0.21). Inferior quadrant was the best RNFL parameter (sensitivity, 74%; specificity, 95.9%; PLR, 18.13; and NLR, 0.27), as was rim area (sensitivity, 68%; specificity, 98%; PLR, 33.3; and NLR, 0.33) among ONH parameters. The or-logic combination of minimum GCIPL and average RNFL provided the overall best diagnostic performance (sensitivity, 94%; specificity, 85.7%; PRL, 6.58; and NLR, 0.07) as compared with the best RNFL, best ONH, and best and-logic combination (minimum GCIPL and inferior quadrant RNFL; sensitivity, 64%; specificity, 100%; PLR, infinity; and NPR, 0.36). CONCLUSIONS The binary or-logic combination of minimum GCIPL and average RNFL or rim area provides better diagnostic performances than those of and-logic combinations or best single GCIPL, RNFL, or ONH parameters. This finding may be clinically valuable for the diagnosis of early glaucoma.

New developments in optical coherence tomography for glaucoma

Purpose of review Structural imaging is becoming a powerful adjunct for the diagnosis and progression of glaucoma. There are several competing technologies in this arena. Optical coherence tomography continues to evolve at a fast pace, so it can be challenging to keep up with the latest information. This review covers the recent papers relevant to optical coherence tomography for glaucoma. Recent findings Retinal nerve fiber layer imaging by optical coherence tomography is reliable. Age, ethnicity, axial length and optic disc size can affect the machines normative range. Scan quality can be affected by movement, media opacities, myopia and severity of disease. The sensitivity and specificity are variable across multiple studies. Despite this, the technology is beginning to help us understand the structure–function relationship in glaucoma. Summary The next generation optical coherence tomography is around the corner. By understanding the current strengths and limitations of this advancing technology, one can better assess its use in clinical practice.

An emerging treatment option for glaucoma: Rho kinase inhibitors.

Rho kinase (ROCK) inhibitors are a novel potential class of glaucoma therapeutics with multiple compounds currently in Phase II and III US Food and Drug Administration trials in the United States. These selective agents work by relaxing the trabecular meshwork through inhibition of the actin cytoskeleton contractile tone of smooth muscle. This results in increased aqueous outflow directly through the trabecular meshwork, achieving lower intraocular pressures in a range similar to prostaglandins. There are also animal studies indicating that ROCK inhibitors may improve blood flow to the optic nerve, increase ganglion cell survival, and reduce bleb scarring in glaucoma surgery. Given the multiple beneficial effects for glaucoma patients, ROCK inhibitors are certainly a highly anticipated emerging treatment option for glaucoma.

Myopia and glaucoma: diagnostic and therapeutic challenges.

Purpose of review There is strong epidemiologic evidence linking myopia with glaucomatous disease, but a myopic optic nerve can pose significant challenges with regard to making the correct diagnosis of glaucoma. This review provides an overview of these diagnostic and therapeutic challenges with a particular focus on how the growing prevalence of myopia among specific populations may impact such therapy. Recent findings For a given individual, the link between myopia and glaucoma remains murky in many circumstances, largely because of the fact that it is difficult to separate out myopia-related structural and functional abnormalities from ‘true’ glaucomatous changes. Using optical coherence tomography (OCT) imaging, myopia has been found to be associated with temporal displacement and thinning of the superior and inferior nerve fiber layer bundles. In particular, sequential generations of ‘Asian’ ethnicities have been noted to demonstrate increasing rates of high myopia at earlier ages, sometimes with associated visual field defects at normal intraocular pressures. As is the case with any progressive condition, it is often not possible to distinguish glaucomatous from nonglaucomatous disease based on a single examination, and thus follow-up with OCT or perimetry from an established baseline is useful. Summary Although myopia is a known risk factor for glaucoma, it may also result in structural and functional defects that cannot be distinguished from those caused by glaucoma based solely on cross-sectional information. Longitudinal observation may be necessary to distinguish among the multiple effects of myopia on the optic nerve and the natural history of glaucoma, which may vary substantially amongst those who are affected.