Richard P. Mills

The Collaborative Initial Glaucoma treatment study: Interim quality of life findings after Initial medical or surgical treatment of Glaucoma

OBJECTIVE To present interim quality of life (QOL) findings in the Collaborative Initial Glaucoma Treatment Study (CIGTS) using all available follow-up through 5 years from treatment initiation. DESIGN Randomized controlled clinical trial. PARTICIPANTS Six hundred seven newly diagnosed patients with open-angle glaucoma from 14 clinical centers. INTERVENTION Patients were randomly assigned to either initial medical therapy or initial trabeculectomy. After treatment initiation and early follow-up, patients received clinical and QOL evaluations at 6-month intervals. QOL assessments were administered by telephone at a centralized interviewing center. MAIN OUTCOME MEASURES The CIGTS collected comprehensive QOL information that included both generic and vision-specific QOL measures. This article focuses on initial treatment group differences related to symptom reporting, as measured by a Symptom and Health Problem Checklist, and changes in daily visual functioning, as measured by the Visual Activities Questionnaire (VAQ). RESULTS Across both treatment groups, there was an overall decline in the percent of participants reporting symptoms over time. Of 43 possible symptoms, 12 symptoms were reported with greater frequency by the surgically treated group and 7 symptoms more frequently by the medically-treated group. The surgical patients reported more total Symptom Impact Glaucoma (P = 0.005) and, in particular, more bother related to local eye symptoms. Very few treatment group differences were noted in visual functioning, although surgical patients reported more problems with activities related to their visual acuity (P = 0.024). The percentage of patients across treatment groups reporting worry about blindness was 50% at baseline but declined to approximately 25% over time. CONCLUSIONS Overall, the QOL impact reported by the two treatment groups as measured by instruments used in this study is remarkably similar, with relatively few significant study group differences observed after up to 5 years of follow-up in the CIGTS. When significant differences in visual function have been detected using the VAQ, they are consistent with the clinical outcomes. To date, the most persistent QOL finding is the increased impact of local eye symptoms reported by the surgical group compared with the medical group. Although no changes are recommended in the treatment of newly diagnosed glaucoma patients at the time of this interim report, further follow-up will allow for more definitive answers to the QOL impact of these two treatment approaches.

Long-term Survival of Molteno Glaucoma Drainage Devices

PURPOSE To evaluate the long-term outcome of the Molteno implant drainage device using survival analysis. METHODS A retrospective chart review was performed on 77 eyes of 71 patients that underwent Molteno implantation for intractable glaucoma unresponsive to conventional management from October 1984 to April 1990 at the University of Washington Eye Center and had at least 6 months of follow-up data. Success was defined as a postoperative intraocular pressure of 22 mmHg or lower with (qualified success) or without (complete success) glaucoma medications and no additional glaucoma surgery, phthisis, or loss of light perception. RESULTS The median follow-up was 44 months (range, 6-107 months). Indications for Molteno implantation were aphakia/pseudophakia (n=24), neovascular glaucoma (n=20), uveitic glaucoma (n=12), failed trabeculectomy (n=9), traumatic glaucoma (n=8), and congenital glaucoma (n=4). The total success was 57% (23% complete; 34% qualified) at the last follow-up. Kaplan-Meier survival curves demonstrated a continuous and relatively linear attrition of success over at least 5 1/2 postoperative years. The uveitic glaucoma group had the highest success rate of 75%. Eyes with neovascular glaucoma failed significantly more frequently than those with uveitic glaucoma (P<0.01). There was no significant difference in outcome based on sex, race, single versus double plate, anterior chamber versus posterior chamber tube placement, or two-stage versus single-stage surgery. Younger age was associated with a significantly higher failure rate after controlling for glaucoma category (P<0.01). CONCLUSION The Molteno implant drainage device offers a reasonable long- term outcome in eyes with intractable glaucomas. However, an ongoing rate of failure, not unlike that seen after other filtration surgery, is to be expected.

Clinical Comparison of the Icare Tonometer and Goldmann Applanation Tonometry

PurposeTo compare a new method of intraocular pressure (IOP) measurement, using the Icare tonometer, with Goldmann applanation tonometry (GAT). Patients and MethodsTwo observers obtained IOP readings in 292 eyes (143 right and 149 left) of 153 subjects, using the Icare without topical anesthetic. A GAT reading was subsequently obtained by a consultant ophthalmologist, without the knowledge of the Icare readings. Central corneal thickness (CCT) was obtained on all eyes with ultrasound pachymetry. Patient comfort after IOP measurement was assessed in a consecutive subset of patients. ResultsThe intraclass correlation coefficient between the 2 modalities of IOP measurement was r=0.95 for the right and r=0.93 for the left eye. The mean difference (Icare−GAT) between the IOP measured by the 2 methods was 0.4 mm Hg in the right eye (SD 3.0, 95% confidence interval −5.5 to 6.3), and 0.8 mm Hg in the left eye (SD 3.0, confidence interval −4.7 to 6.2). GAT measurements did not vary with CCT [correlation coefficient=0.09 (P=0.25) right and 0.14 (P=0.09) left eyes]. However, IOP measured with Icare tonometry increased with increasing CCT [correlation coefficient=0.16 (P=0.05) right and 0.21 (P=0.01) left eyes]. For every 100-μm increase in CCT, the difference (Icare−GAT) increased by 1 mm Hg. Of the 38 consecutive patients surveyed, 28 (73.7%) rated the Icare more comfortable than GAT, with only 2 (5.3%) rating it less comfortable (P<0.001). ConclusionsThere is good correlation between the 2 methods of IOP measurement, even at extremes of IOP. The Icare instrument was easy to use and recorded rapid and consistent readings with minimal training. It seems to be more comfortable than GAT and obviates the need for topical anesthesia.

Esterman Disability Rating in Severe Glaucoma

Forty-two patients with severe visual loss from glaucoma were assigned an Esterman visual function score according to their performance on a binocular visual field test using an automated perimeter. (The Esterman score has been adopted by the AMA as a new standard for rating visual field disability.) The visual function score was correlated with patient responses to questions about perceived visual disability. Monocular visual field results from both eyes using automated suprathreshold static and manual kinetic perimetry were also compared to the binocular Esterman test results. The binocular Esterman test rapidly provided information concerning visual field disability which correlated well with combined monocular results, and with an objectivity lacking in patient responses to a disability questionnaire.

Association of TCF4 and CLU polymorphisms with Fuchs endothelial dystrophy and implication of CLU and TGFBI proteins in the disease process

Fuchs’ endothelial dystrophy (FED) is a disease affecting the corneal endothelium. Recent studies reported significant association of polymorphisms in the TCF4 (transcription factor 4) gene, and a borderline association of PTPRG (protein tyrosine phosphatase, receptor type, G) variants with late-onset FED in Caucasians from the United States. Association of TCF4 has also been reported in the Chinese population. We aimed to determine association of the reported polymorphisms in TCF4 and PTPRG, and association of polymorphisms in the candidate genes ZEB1 (zinc-finger E-box binding homoebox 1), COL8A2 (collagen, type VIII, alpha 2), TGFBI (transforming growth factor, β-induced) and CLU (clusterin) in Australian cases. We also compared the expression of TGFBI and CLU proteins between FED and normal whole corneas. In all, 30 single-nucleotide polymorphisms (SNPs) from the candidate genes were genotyped in 103 cases and 275 controls. Each SNP and haplotype was assessed for association with the disease. SNP analysis identified an association of TCF4 (rs613872 (P=5.25 × 10−15, OR=4.05), rs9954153 (P=3.37 × 10−7, OR=2.58), rs2286812 (P=4.23 × 10−6, OR=2.55) and rs17595731 (P=3.57 × 10−5, OR=3.79)), CLU (rs17466684; P=0.003, OR=1.85) and one haplotype of TGFBI SNPs (P=0.011, OR=2.29) with FED in Caucasian Australians. No evidence for genetic association of PTPRG, ZEB1 and COL8A2 was found. Immunohistochemistry showed differential expression of CLU and TGFBI proteins in FED-affected compared with normal corneas. In conclusion, variation in TCF4, CLU and TGFBI, but not PTPRG, ZEB1 and COL8A2 genes are associated with FED in Caucasian Australian cases. Differential expression of CLU and TGFBI proteins in FED-affected corneas provides novel insights into the disease mechanism.

Gaze-evoked amaurosis

Gaze-evoked amaurosis is a transient monocular loss of vision occurring in a particular direction of eccentric gaze. Six cases are reported with a mean follow-up of 5 years; three with optic nerve sheath meningiomas and three with orbital cavernous hemangiomas. Five of the six patients have had no visual deterioration during follow-up. Bilateral optic nerve sheath meningiomas led to visual deterioration in both eyes of one patient, but gaze-evoked amaurosis was present in only one eye. The symptom of gaze-evoked amaurosis, while alarming, is not predictive of permanent visual loss. Possible mechanisms for gaze-evoked amaurosis include inhibition of axonal impulses or transient optic nerve ischemia.

Glaucoma screening using the scanning laser polarimeter.

Purpose: To determine the ability of scanning laser polarimetry (GDx Nerve Fiber Analyzer; Laser Diagnostic Technologies, Inc., San Diego, CA) to separate normal eyes and those considered likely to have glaucoma in a public glaucoma screening. Methods: A 2‐day public glaucoma screening program was held at two different institutions. Each subject underwent ophthalmologic examination, Humphrey perimetry (24–2 Fastpac program), and imaging using scanning laser polarimetry (GDx) in each eye for allocation into a diagnostic category: normal, ocular hypertensive, glaucoma suspect, or glaucoma. Results from the normal and glaucoma groups were analyzed, using modulation parameters calculated from a measurement band located 1.8 disc diameters from the disc, and selected parameters provided automatically by GDx software. Receiver operating characteristic curves were used to depict the sensitivity/specificity relationship at different GDx parameter cutoff levels. Results: Of 200 subjects, 197 were classified; 122 were classified as normal, 23 were classified with ocular hypertension, 30 were classified as glaucoma suspects, and 22 were classified with definite glaucoma. Three subjects had ocular diseases other than glaucoma. The maximum area under the receiver operating characteristic curve for modulation parameters was 0.935, and for the GDx software parameters was 0.901. Conclusions: Scanning laser polarimetry may be useful in glaucoma screening.

Correlation of peripapillary nerve fiber layer thickness by scanning laser polarimetry with visual field defects in patients with glaucoma.

PurposeTo assess the correlation between the results of peripapillary scanning laser polarimetry of the retinal nerve fiber layer (NFL) and automated visual field testing in patients with open-angle glaucoma. MethodsVisual fields from 42 patients with varying stages of glaucoma were scored using Collaborative Initial Glaucoma Treatment Study (CIGTS) criteria. Mean deviation, pattern standard deviation, and CIGTS total and hemifield visual field scores were correlated with peripapillary NFL thickness measured by scanning laser polarimetry using summed, ratio-based, and modulation parameters. ResultsMean deviation and CIGTS total and upper hemifield score were significantly correlated with NFL retardation values using summed, ratio-based, or modulation parameters. The CIGTS lower hemifield score was significantly correlated with modulation parameter values only. Correlation of CIGTS scores was significantly stronger with modulation parameters than with summed parameters (total and lower hemifield scores) and ratio-based parameters (lower hemifield only) by the Hotelling t test. ConclusionRelative NFL thickness measured by scanning laser polarimetry correlates well with visual field defects seen on Humphrey perimetry of patients with open-angle glaucoma. Modulation parameters, in which the superior and inferior peak NFL thickness (as measured by scanning laser polarimetry) are adjusted for the patients average minimum NFL thickness in the nasal and temporal quadrants, provided stronger correlation than summed parameters and ratio-based parameters.

The Natural History and CT Appearance of Acquired Hyperopia with Choroidal Folds

Seven healthy adults with acquired hyperopic change in refractive error had choroidal folds in affected eyes. High resolution computerized tomographic scanning techniques used to obtain coronal, oblique coronal, and parasagittal reformations revealed flattening of the posterior globes and mild to moderate optic nerve enlargement. In 5 of 11 eyes, a space was noted between the optic nerve and its sheath, implying expansion of the sub-arachnoid perineural compartment. The clinical findings and natural history of this syndrome, based on an average follow-up of 4.5 years, are discussed.

Reduced intraocular pressure and increased ocular perfusion pressure in normal tension glaucoma: a review of short-term studies with three dose regimens of latanoprost treatment.

Currently used ocular hypotensive agents do not effectively lower intraocular pressure (IOP) in some normal-tension glaucoma (NTG) patients. The prostaglandin F2 alpha analogue, latanoprost, has been shown to reduce IOP in normal subjects and ocular hypertensive glaucoma patients by increasing uveoscleral outflow. This mechanism is expected to be particularly effective in the lower IOP range that is typical of NTG. To date, three dose regimens of latanoprost have been shown to reduce IOP significantly in NTG. The IOP reductions of 14.2% and 15% obtained with twice-daily application of 0.0015% and 0.006% latanoprost, respectively, were comparable to the modest IOP reduction that has been reported for other glaucoma drugs in NTG. In contrast, once-daily application of 0.005% latanoprost resulted in a 21.4% IOP reduction. In another study that included 24-hour monitoring of systemic blood pressure and heart rate in NTG patients, the ocular perfusion pressure was found to improve more on once-daily 0.005% latanoprost than on twice-daily treatment with 0.5% timolol. Thus, once-daily 0.005% latanoprost appears to be a more effective and more convenient ocular hypotensive agent for treating NTG than currently used glaucoma drugs. However, long-term studies will ultimately be needed to establish the efficacy of this new drug to delay or prevent the progression of visual field loss in normal tension glaucoma.