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Risk Factors for Visual Field Progression in Treated Glaucoma

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Risk Factors for Visual Field Progression in Treated Glaucoma CLINICAL SCIENCES Risk Factors for Visual Field Progression in Treated Glaucoma Carlos Gustavo V. De Moraes, MD; Viral J. Juthani, MD; Jeffrey M. Liebmann, MD; Christopher C. Teng, MD; Celso Tello, MD; Remo Susanna Jr, MD; Robert Ritch, MD Objective: To determine intraocular pressure (IOP)– was 11.1 (3.0), spanning a mean (SD) of 6.4 (1.7) years. dependent and IOP-independent variables associated with In the univariable model, older age (odds ratio [OR], 1.19 visual field (VF) progression in treated glaucoma. per decade; P=.01), baseline diagnosis of exfoliation syn- drome (OR, 1.79; P=.01), decreased central corneal thick- Design: Retrospective cohort of the Glaucoma Progres- ness (OR, 1.38 per 40 µm thinner; PϽ.01), a detected sion Study. disc hemorrhage (OR, 2.31; PϽ.01), presence of beta- zone parapapillary atrophy (OR, 2.17; PϽ.01), and all Methods: Consecutive, treated glaucoma patients with IOP parameters (mean follow-up, peak, and fluctua- repeatable VF loss who had 8 or more VF examinations tion; PϽ.01) were associated with increased risk of VF of either eye, using the Swedish Interactive Threshold Al- progression. In the multivariable model, peak IOP (OR, gorithm (24-2 SITA-Standard, Humphrey Field Ana- 1.13; PϽ.01), thinner central corneal thickness (OR, 1.45 lyzer II; Carl Zeiss Meditec, Inc, Dublin, California), dur- per 40 µm thinner; PϽ.01), a detected disc hemorrhage ing the period between January 1999 and September 2009 (OR, 2.59; PϽ.01), and presence of beta-zone parapap- were included. Visual field progression was evaluated illary atrophy (OR, 2.38; PϽ.01) were associated with using automated pointwise linear regression. Evaluated VF progression. data included age, sex, race, central corneal thickness, baseline VF mean deviation, mean follow-up IOP, peak Conclusions: IOP-dependent and IOP-independent risk IOP, IOP fluctuation, a detected disc hemorrhage, and factors affect disease progression in treated glaucoma. Peak presence of beta-zone parapapillary atrophy. IOP is a better predictor of progression than is IOP mean or fluctuation. Results: We selected 587 eyes of 587 patients (mean [SD] age, 64.9 [13.0] years). The mean (SD) number of VFs Arch Ophthalmol. 2011;129(5):562-568 HE NATIONAL INSTITUTES OF providing clinicians with information on the Health randomized clini- extent to which these prospective, well- cal trials (RCTs) of glau- designed trials can be applied to a real- coma treatment have word population. The purpose of our study helped elucidate the main is to verify whether the main risk factors Trisk factors for the development and pro- identified in populations enrolled in the gression of the disease, one of the major major RCTs can also be applied to popula- causes of irreversible blindness world- tions seen in scenarios that more closely wide.1-7 Yet, the patient populations in resemble a typical clinical practice. these RCTs may not resemble the major- ity of patients, and their protocol designs METHODS may not resemble the clinical conduct typi- 8-12 cally seen in clinical practice. Our study was approved by the New York Eye Author Affiliations: Einhorn and Ear Infirmary institutional review board and Clinical Research Center, New CME available online at followed the tenets of the Declaration of Hel- York Eye and Ear Infirmary www.jamaarchivescme.com sinki. We included subjects from the New York (Drs De Moraes, Liebmann, and questions on page 543 Glaucoma Progression Study who were evalu- Teng, Tello, and Ritch) and New ated in the glaucoma referral practice of three York University School of Retrospective cohort studies have inher- of us (J.M.L., R.R., and C.T.) between January Medicine (Drs De Moraes, ent disadvantages compared with RCTs, 1999 and September 2009. After an initial visit Juthani, Liebmann, and Teng), mostly due to nonstandardized therapy, the consisting of a complete ophthalmologic ex- New York, and New York amination, standard achromatic perimetry (24-2 Medical College, Valhalla presence of various glaucoma phenotypes, SITA-Standard, Humphrey Field Analyzer II; (Drs Teng, Tello, and Ritch); lack of stringent reliability criteria for struc- Carl Zeiss Meditec, Inc, Dublin, California), and and University of São Paulo tural or functional testing, and decreased fre- optic disc stereophotographs, patients were re- School of Medicine, São Paulo, quency of testing. Nonetheless, large, ret- examined, usually at 3- to 6-month intervals, and Brazil (Dr Susanna). rospective cohorts have the potential of the same tests repeated within 6 to 12 months. ARCH OPHTHALMOL / VOL 129 (NO. 5), MAY 2011 WWW.ARCHOPHTHALMOL.COM 562 ©2011 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/29/2021 Corrected on May 11, 2011 We included patients with glaucomatous optic neuropathy and have on the final average, we used the average IOP for each repeatable visual field (VF) loss who had 8 or more VF exami- 6-month period following enrollment to calculate the mean fol- nations of either eye, using the Swedish Interactive Threshold Al- low-up IOP. Intraocular pressure fluctuation was defined as the gorithm (24-2 SITA-Standard, Humphrey Field Analyzer II) be- standard deviation of this value. Intraocular pressure covariance cause a greater number of VF tests increases the sensitivity and was calculated by dividing the standard deviation IOP by the mean specificity of pointwise linear regression analysis in detecting pro- IOP and then multiplying by 100. We excluded all IOP measure- gression.13,14 All eligible eyes were required to have best- ments occurring 4 weeks after any type of incisional surgery or corrected visual acuity of 20/40 or better at baseline and a spheri- laser procedure to avoid the effect of transitory IOP changes that cal equivalent of less than 6 diopters. If both eyes of the same patient often occur during this period. Central corneal thickness (CCT) were eligible, the eye with the greater number of VF tests was se- was measured using ultrasonic pachymetry (DGH-550; DGH Tech- lected. We excluded subjects with optic disc photographs of poor nology Inc, Exton, Pennsylvania). Exfoliation syndrome was de- quality, subjects who were unfamiliar with static perimetry, sub- fined as the presence of characteristic exfoliation material on the jects without reliable baseline results of standard automated pe- pupil border or on the lens capsule following pupil dilation. rimetry, and subjects whose conditions (other than glaucoma and mild cataract) would likely affect VF testing. STATISTICAL ANALYSIS DISC PHOTOGRAPH REVIEW Categorical variables were compared using the ␹2 test. Inde- pendent-samples t tests were used for comparisons of continu- Disc photographs of patients in this cohort were reviewed by ous variables between groups. Pearson correlation coeffi- 2 masked glaucoma specialists searching for disc hemorrhage ␤ cients (r) were calculated to assess the relationship between (DH) and beta-zone parapapillary atrophy ( PPA) using a slide different IOP parameters. First, a logistic regression was used projector. A DH was defined as a splinter-like or flame-shaped to evaluate the effect of each IOP parameter on the predefined hemorrhage on or within the retinal nerve fiber layer or neu- 15,16 progression outcome. Because greater follow-up time in- roretinal rim. Parapapillary atrophy was defined as an creases the likelihood of detecting progression,13,14 all analy- inner crescent of chorioretinal atrophy with visible sclera and ␤ ses were time adjusted. Also, because IOP-lowering interven- choroidal vessels ( PPA) and an outer irregular area of hypo- tions may affect the IOP variability,21,22 the model was adjusted pigmentation and hyperpigmentation (alpha-zone PPA).17,18 The ␤ for the occurrence of any type of glaucoma-filtering proce- presence of DH and PPA at any time in the photographs re- dure during follow-up. Then, the IOP parameter that best cor- viewed was reported. In cases in which the investigators dis- related with a progression end point was entered in the model agreed, a third investigator was used for adjudication. that included all evaluated factors. Each variable was first tested in a univariable model. Those with PϽ.25 were then entered VISUAL FIELD ANALYSIS in the multivariable analysis. The multivariable model was per- formed using a stepwise approach; that is, significant vari- A glaucomatous VF was defined if a patient had a glaucoma hemi- ables (PϽ.05) were entered sequentially. Statistical signifi- field test result that was outside the normal limits or if the pat- cance was defined at PϽ.05 in the final model. tern standard deviation was triggered at PϽ.05 on at least 2 con- secutive baseline VF tests. The 2 baseline tests required reliability RESULTS indices better than 25% in order to be included. Automated point- wise linear regression analysis was performed using Progressor version 3.3 software (Medisoft, Ltd, Leeds, England), providing We selected 587 eyes of 587 patients. Their mean (SD) slopes (in units of decibels per year) of progression both glob- age at baseline assessment was 64.9 (13.0) years. The mean ally and locally for each point based on threshold sensitivity maps, (SD) number of evaluated VFs was 11.1 (3.0) (range, as well as its level of significance (P values). Details of the soft- 8-24), spanning a mean (SD) of 6.4 (1.7) years (range, ware have been described elsewhere.19 All patients were famil- 2.0-10.2 years). More often they were women (58%) and iar with 24-2 achromatic perimetry prior to enrollment. Pro- of European ancestry (90%). The most common diag- gression was defined as the presence of a test point with a slope nosis was primary open-angle glaucoma (46%) (Table 1). of sensitivity over time of a greater than 1.0-dB loss per year, with PϽ.01.
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