The patient's journey: glaucoma.
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Biomedical subjects
Publications and source records attributed to Douglas J Rhee.
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PURPOSE: Topiramate-induced angle-closure glaucoma (TiACG) is believed to be related to its sulfonamide moiety. Although the exact mechanism is unknown, the time course and constellation of symptoms are consistent with a possible inflammatory pathophysiologic condition. DESIGN: Interventional case report. METHODS: We report the clinical outcome of a case of TiACG that was associated with an extreme intraocular pressure elevation of >60 mm Hg that was treated with the combination of systemic mannitol and methylprednisolone. RESULTS: The combination of the two systemic medications resulted in the resolution of the attack with a much more rapid time course than is seen typically for extreme cases of TiACG. Mannitol treatment alone did not lower the intraocular pressure after 90 minutes, although improvement was noted four hours after methylprednisolone. CONCLUSION: For severe cases of TiACG that are associated with very high intraocular pressures, the combination of mannitol and methylprednisolone can induce a rapid improvement. Inflammation may be a component of TiACG.
PURPOSE: This study was designed to report the long-term complications of iris-claw phakic intraocular lens implantation in a patient with Weill-Marchesani syndrome. METHODS: Case report and literature review. RESULTS: A 26-year-old man with a history of glaucoma had bilateral phakic lens implantation for high myopia 10 years previously. Two years later, the left implant dislocated and was repositioned. Slit-lamp examination of both eyes revealed phakic implants of the iris-claw variety. There were moderate iridocorneal adhesions in the areas in which the lens haptics pinched the iris in both eyes and moderate epithelial and stromal edema over the temporal one-third of the left cornea. The crystalline lenses were clear with 3+phacodonesis OU. Dilated fundus examinations revealed bilateral severe optic nerve cupping. Crystalline lens diameters were measured at 7.5mm in the right eye and 8 mm in the left. Anterior chamber depths were 2.63 mm OD and 2.40 mm OS. Specular microscopy revealed central endothelial cell counts of 1133 and 587 cells/mm OD and OS, respectively. Axial lengths were 23.3 mm OD and 25 mm OS. Gonioscopic examination revealed bilateral angle closure with marked peripheral anterior synechiae. Based on our findings of short stature, shortened and thickened fingers, relatively normal axial length, microspherophakia, high myopia, and glaucoma, we diagnosed the patient with Weill-Marchesani syndrome. CONCLUSION: Iris claw-lens phakic lenses may be an effective surgical alternative to correct high myopia in select patients; however, it may produce long-term complications in eyes with specific features.
PURPOSE OF REVIEW: The detection of optic disc and retinal nerve fiber layer damage and change is the cornerstone of glaucoma management. Assessment of the retinal nerve fiber layer for localized and diffuse damage has been traditionally based on clinical examination, with documentation of change primarily qualitative. With the latest improvements in optical imaging instruments, objective and quantitative measurements of the retinal nerve fiber layer are now possible. This review summarizes the results from recent cross-sectional studies evaluating the discriminating ability of automated retinal nerve fiber layer measurements to detect glaucoma, and from longitudinal studies assessing the ability to predict and monitor glaucomatous changes. RECENT FINDINGS: Numerous cross-sectional studies have documented good diagnostic accuracy of a scanning laser polarimeter (GDx VCC), the optical coherence tomograph (Stratus), and the Heidelberg Retina Tomograph retinal nerve fiber layer measurements for differentiating between healthy and glaucoma eyes. There are only limited data available on the ability of these retinal nerve fiber layer measurements to document change over time. SUMMARY: It is essential that the clinician understand the specific strengths and weaknesses of each technique so that only good quality retinal nerve fiber layer information will be used in conjunction with careful clinical examination and visual function testing for glaucoma management decisions. Longitudinal studies are needed to evaluate the ability of these instruments to document retinal nerve fiber layer change over time.
PURPOSE: Our purpose was to evaluate the accuracy of self-reporting of the prescribed medication regimen in a glaucoma population, identify contributing factors, and assess the effect of written instructions. METHODS AND MATERIALS: All patients at an urban resident glaucoma clinic were offered participation in this prospective, case-controlled study. Two trained interviewers administered a confidential questionnaire consisting of six questions regarding the name and dosage of ophthalmic medications, education level, ability to read, and age. A verbatim response for each question was recorded on the questionnaire. At the end of the visit, patients were given a written chart describing their ophthalmic medications, frequency, and dosage. At their next scheduled visit, the same questionnaire was repeated. The patients' responses from both visits were compared with the regimen they were prescribed and with each other. This information was used to determine the accuracy of reporting medications. RESULTS: A total of 193 patients were enrolled in the study over a 10-month period; 164 patients completed both phases (85% completion rate). The study population consisted of 85 women and 79 men with a mean age of 68.40+/-11.6 years. Eighty-four patients had attained less than 12th grade education and 80 had completed high school. At the first visit, 66 patients (40%) showed less than 100% accuracy. Forty-nine of 84 (58%) patients who had not completed high school education showed less than 100% accuracy with a mean score of 65% (P=0.001), whereas 17 of 80 (21%) of patients who had completed high school showed less than 100% accuracy with a mean score of 87% (P=0.001). After written instruction, the accuracy of reporting improved by 23.36+/-30.8 percentile points in patients without completion of high school education and improved by 8.46+/-21.7 percentile points in patients who had completed high school (P<0.001). The mean number of ophthalmic medications prescribed was 2.10+/-0.93 (range 1 to 4). Patients on one medication had 100% accuracy in reporting 82% of the time, whereas those with four medications had 100% accuracy 21% of the time. Gender, age, and race of the patient were not correlated with the accuracy of self-reporting (P>0.05). CONCLUSION: The education level of the patient and the number of medications showed direct correlation with patients' ability to report medications accurately. Patients showed improvement in accuracy of reporting medications when given written instructions about their regimen, regardless of their level of education or number of medications.
PURPOSE: The purpose of the study was to ascertain the prevalence of plateau iris syndrome in the first-degree relatives of those patients affected with plateau iris syndrome. METHODS: All patients seen with plateau iris syndrome over a 5-year period were identified. These patients were approached for participation and first-degree family members above 18 years of age were screened. All people identified with plateau iris configuration underwent ultrasound biomicroscopy to document and confirm the angle configuration and subsequent gonioscopy after laser iridotomies. RESULTS: Sixteen patients were identified; 3 refused to participate, 2 were unable to be contacted, and 1 withdrew after initially consenting to participate. In this case, the patient agreed to participate, but all her living first-degree family members refused to be screened. Among the 10 patients whose living first-degree relatives were screened, we found 5 families with at least 1 additional first-degree family member having plateau iris syndrome. CONCLUSIONS: Some families have more than 1 member with plateau iris syndrome. The pattern of inheritance resembles an autosomal dominant pattern with incomplete penetrance.
PURPOSE: To determine the effect of latanoprost on the expression of human matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the ciliary body. METHODS: Total RNA was isolated, and qualitative RT-PCR was performed to detect the mRNA of MMPs and TIMPs in human ciliary body tissue and explant cultures of ciliary body smooth muscle (CBSM) cells. CBSM cell cultures were treated with vehicle control or latanoprost acid for 24 hours. Quantitative RT-PCR of cell cultures from five different donors was performed to determine relative changes in expression. GAPDH served as an endogenous control. RESULTS: The mRNA of MMP-1, -2, -3, -11, -12, -14, -15, -16, -17, -19, and -24 as well as TIMP-1 to -4 were found in ciliary body tissue and CBSM cells. MMP-9 was present after latanoprost treatment. In control CBSM cells, the relative expression of MMP mRNA was MMP-2 and -14 > MMP-24 > MMP-1, -11, -15, -16, and -19 > MMP-3 and 17, > MMP-12. The relative expression of TIMP mRNA was TIMP-2 > TIMP-1 > TIMP-3 > TIMP-4. Latanoprost increased MMP-3 (in three of five cultures), MMP-17 (in four of five cultures), and TIMP-3 (in all five cultures); MMP-1, -2, -12, -14, -15, and -16 and TIMP-4 were downregulated. CONCLUSIONS: The transcription of the genes for MMP-3 and -17 is increased by latanoprost treatment. MMP-9 is present after latanoprost treatment and may also mediate ECM changes. TIMP-3 is upregulated and may compensate for the increase in MMPs. These coordinated changes could be expected to mediate the latanoprost-induced alteration of ECM in the ciliary body.
PURPOSE: To determine the effect of latanoprost on the expression of human matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the trabecular meshwork (TM). METHODS: Total RNA was isolated, and qualitative RT-PCR was performed to detect the mRNA of MMPs and TIMPs in human TM tissue and explant cultures of TM endothelial cells. Cultures of TM cells were treated with vehicle control or latanoprost acid for 24 hours. Real-time RT-PCR of cell cultures from five different donors was performed to determine relative changes in expression. GAPDH served as an endogenous control. RESULTS: The mRNA of MMP-1, -2, -3, -11, -12, -14, -15, -16, -17, -19, and -24 and of TIMP-1 to -4 was present in TM tissue and cultures of TM cells. MMP-9 was not found. In control TM endothelial cells, the relative expression of MMP mRNA were MMP-2 and -14 > MMP-16, -19, and -24 > MMP-15 > MMP-11 and -17 > MMP-1 and -3 > MMP-12. The relative expressions of TIMP mRNA were TIMP-1 > TIMP-2 and -3 > TIMP-4. Latanoprost increased MMP-1 (in four of five cultures), MMP-3 (in four of five cultures), MMP-17 (in three of five cultures), MMP-24 (in all five cultures), TIMP-2, -3, and -4 expression (in three of five cultures); MMP-11 and -15 were downregulated. CONCLUSIONS: Contrary to the expected result, latanoprost seems to have a significant effect on TM cells. The transcription of the genes for MMP-1, -3, -17, and -24 is increased by latanoprost treatment. TIMP-2, -3, and -4 are also upregulated. The upregulation of these TIMPs may compensate for the increase of those MMPs. The absence of MMP-9 and concurrent upregulation of a greater number of TIMPs may explain the limited effect of latanoprost on TM outflow.
PURPOSE: To evaluate the clinical indications and postoperative results of iris-sutured posterior chamber intraocular lens implants performed during penetrating keratoplasty. METHODS: Medical records were retrospectively reviewed for preoperative indications and postoperative results of 342 consecutive patients (366 eyes) who underwent iris suturing of a posterior chamber intraocular lens implant during penetrating keratoplasty over a 9-year period. RESULTS: Mean follow-up was 36 months. The principal indications for corneal transplantation were pseudophakic and aphakic bullous keratopathy. Mean postoperative best spectacle-corrected visual acuity was better than preoperatively at all measured time points (P < 0.0001) and improved from 20/474 preoperatively to 20/85 at 1 year. Nine eyes (7.7%) with known preoperative glaucoma required escalation of therapy by medication or surgery to control the intraocular pressure. Seventy-two eyes (29%) without known preoperative glaucoma required treatment of elevated intraocular pressure. Seventy-nine eyes (28%) without known preoperative cystoid macular edema were additionally diagnosed. Mean endothelial cell counts declined throughout the study time frame. Corneal donor rejection episodes occurred in 36 (9.8%) eyes, with the majority having a single episode. Overall, 27 (7.4%) eyes had known graft failure at last follow-up. Two eyes (0.5%) were enucleated following wound disruption. CONCLUSIONS: These long-term results of iris-sutured posterior chamber intraocular lens implants performed during penetrating keratoplasty suggest acceptable visual acuity, graft survival, and complication rates. They are similar to published retrospective and prospective results of flexible open-loop anterior chamber and transsclerally-sutured posterior chamber intraocular lens implants placed during penetrating keratoplasty.
The human trabecular meshwork (TM) is the major site of resistance for aqueous humor outflow. The purpose of this investigation was to determine the suitability of TMs harvested from donor corneoscleral buttons (buttons) for laboratory studies. Histologic examination using light and electron microscopy was performed. Additionally, the effect of incubation in serum free media on histologic appearance was studied. Total RNA extraction was performed on 45 buttons and four whole eyes. Some TMs were used as a source for establishing primary cell cultures of TM endothelial cells. Compared with donor whole eyes, light microscopy showed comparable TM cellularity in the juxtacanalicular and corneoscleral TM; there was some loss of cells in the inner portion of uveal TM that was adjacent to the anterior chamber. The TM cells appeared healthy and structurally normal on transmissive electron microscopy. Usable quantities of total RNA could be extracted from buttons that had been stored up to 5 weeks. The amount of total RNA extracted correlated well with the histologic appearance. Incubation in serum free media did not have an effect on the histologic appearance. All attempts at establishing primary cell cultures were successful. Unused, donor corneoscleral buttons are an excellent source of TM.
PURPOSE: This investigation was undertaken to determine whether the matricellular protein SPARC is expressed in the human trabecular meshwork (TM) and cultured human trabecular meshwork cells. METHODS: Human donor trabecular meshwork and cultured cells obtained from trabecular meshwork were used in this study. Total RNA was obtained from TM and cultured TM endothelial cells, and RT-PCR was done with primers specific for SPARC. Western blotting was performed on donor TMs using an anti-SPARC monoclonal antibody prepared against rHuSPARC. Confocal microscopy was used to determine the distribution of SPARC in human anterior segments, and immunofluorescence on cultured TM cells was performed with the anti-SPARC antibody. RESULTS: SPARC mRNA was expressed both in TM and in cultured TM cells. Immunoblotting for SPARC showed a doublet with a molecular mass approximately 43 kDa. The ratio of the doublet bands varied with each of the samples; some of the cultured cells and the tissue samples exhibited more of the upper band, and other cultured cells contained almost equal amounts of the two bands. The upper band was shown to be a glycosylated form of SPARC. Immunofluorescence showed that SPARC was expressed in the cultured TM, and confocal microscopy with the anti-SPARC antibody demonstrated the presence of this protein in the TM and in other tissues in the anterior segment. CONCLUSIONS: Our data conclusively show that SPARC mRNA and protein are present in non-glaucomatous TM tissue and in cultured TM cells. Because of its effect on matrix metalloproteinases, SPARC may play a role in the regulation of intraocular pressure.
PURPOSE OF REVIEW: This report briefly reviews recent instruments designed to test the visual function and quality of life of patients with glaucoma. RECENT FINDINGS: Several investigators have examined the functional status and vision-related quality of life among patients with glaucoma. These studies have shown that patients with glaucoma experience diminished visual function and poorer quality of life. SUMMARY: Because glaucoma and its treatment, either medical or surgical, can affect global quality of life as well as vision-related functioning, the assessment of both general and visual system health status is relevant.
OBJECTIVES: To estimate the prevalence of complementary and alternative medicine (CAM) for glaucoma, explore possible demographic and disease-related associations, and inquire about the perceived benefit of these treatments. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: One thousand twenty-seven consecutive patients from two urban, referral glaucoma practices. MAIN OUTCOME MEASURE: Use of CAM specifically for glaucoma. RESULTS: The response rate was 97.4%. The percentage of people reporting use of CAM for glaucoma was 5.4% (54 of 1000 subjects) with 32 of these 54 (59%) having used more than one type. The percentages of those using the various types of nontraditional medicine were: megavitamin therapy (62.9%), herbal therapy (57.4%), exercise (24.0%), diet modification (22.2%), meditation, (1.8%), acupuncture (1.8%), faith healing (1.8%), and homeopathic remedies (1.8%). Patients who used CAM were more likely to be educated beyond high school (P = 0.0014) and less likely to be retired (P = 0.0053). Use of nontraditional therapy was not strongly associated with race (P = 0.044), age (P = 0.062), gender (P = 0.24), length of diagnosis (P = 0.91), or number of glaucoma medications (P = 0.58). Of those using nontraditional therapy, 52% believed that it was helpful, 39% were unsure, and 9% considered it not helpful; 72% discussed their use with an ophthalmologist. Seventy percent discovered it from sources other than providers of either traditional or nontraditional care. CONCLUSIONS: The prevalence of CAM use for glaucoma was 5.4% (95% confidence interval, 4.0%--6.4%). Most glaucoma patients currently cared for by ophthalmologists do not use nontraditional medicine.
PURPOSE: To investigate the expression and secretion of macrophage migration inhibitory factor (MIF) in human trabecular meshwork (HTM) and evaluate its role in ocular inflammation. METHODS: Tissue samples of HTM cells were isolated from donor human eyes or corneoscleral buttons, and the HTM cells were cultured. The expression of MIF on HTM cells was evaluated by RT-PCR, Western blot analysis, and ELISA. T-cell clones (TCCs) were established from ocular infiltrating cells of patients with uveitis. ELISA was used to evaluate the pathologic role of MIF, in relation to regulatory effects on cytokine production by T cells. RESULTS: MIF was detected in the HTM by RT-PCR and Western blot analysis. MIF was also shown by ELISA to be secreted by the HTM cells in culture. The HTM supernatant enhanced IFN-gamma production by TCCs, but not IL-10; and these effects were neutralized by anti-MIF antibodies. Similarly, recombinant MIF enhanced the IFN-gamma production by the TCCs. CONCLUSIONS: MIF is expressed and secreted in the HTM, and MIF has the capacity to enhance T helper 1 cytokines and may play a role as an inflammatory cytokine in the eye.
OBJECTIVE: To assess the reproducibility of retinal nerve fiber layer measurements in pseudophakic normal and glaucomatous eyes using scanning laser polarimetry (GDx, Laser Diagnostic Technologies, Inc., San Diego, CA). PATIENTS AND METHODS: Normal and glaucomatous patients with polymethylmethacrylate posterior chamber intraocular lenses that satisfied entry criteria underwent imaging by two experienced operators. Eyes with posterior capsule opacification or vision less than 20/30 were excluded. Baseline images (mean pixel SD less than 8 mm) were obtained on 3 separate days within a 7-week period. Reproducibility, defined as the pooled within eye variance of these 3 measurements and the coefficient of variation for 12 retardation parameters generated by GDx software were calculated. RESULTS: Eighteen eyes (11 glaucoma, 7 normal) of 15 patients (7 female, 8 male) were enrolled (mean age 78 +/- 6 years). Among glaucomatous eyes, the average mean deviation and corrected pattern standard deviation using achromatic automated perimetry (Zeiss-Humphrey, Dublin, CA) was -3.8 +/- 1.5 dB (range, -1.89 to -5.04 dB) and 4.9 +/- 3.3 dB (range 0 to 11.05 dB), respectively. Coefficient of variation was 10% or less for all retardation parameters except ellipse modulation (20.2%) and neural network number (12.4%). Glaucomatous and normal eyes had similar variability for 8 of 12 (66.7%) retardation parameters. Inferior ratio, ellipse modulation, and superior ratio were significantly less variable in glaucomatous eyes (P = 0.007, 0.02, and 0.04 respectively) than normal eyes. Superior integral was more variable in glaucomatous eyes (P = 0.03). CONCLUSION: Retardation measurements may be obtained in pseudophakic eyes with acceptable reproducibility. Normal eyes and eyes with mild glaucomatous damage have similar variability for most retardation parameters.