Clinical outcomes of gamma-irradiated sterile cornea in aqueous drainage device surgery: a multicenter retrospective study.

PurposeThe purpose of the study was to evaluate the safety and efficacy of gamma-irradiated sterile cornea (GISC) for covering the tube in aqueous drainage device (ADD) surgery in a retrospective, multicenter case series.Patients and methodsParticipants included 297 patients (321 procedures) who had undergone ADD surgery for the first time using GISC patch at three clinic centers in the United States between April 2009 and July 2012. The medical records of those consecutive patients were reviewed. Preoperative, intraoperative, and postoperative parameters about GISC were collected and analyzed. The main outcome measures were patch graft failure (PGF) and postoperative complications related to GISC.ResultsThree hundred and nineteen eyes in 295 patients were included in the current analysis. Ten out of the 319 eyes experienced PGF with a mean follow-up of 15.4±9.8 (SD) months. The overall cumulative PGF proportion from Kaplan-Meier analysis was 2.6% (95% CI: 0.6-4.7%) at 18 months. We detected two cases of presumed endophthalmitis related to PGF.ConclusionsGISC appears to have a reasonable success rate for preventing tube exposure related to PGF over an 18-month period. This success rate, in combination with other features of GISC (transparency and storage at room temperature), makes it a viable choice for patch graft material during ADD.

Risk factors for late-onset infection following glaucoma filtration surgery.

OBJECTIVE: To determine the risk factors for late-onset infection following glaucoma filtration surgery. METHODS: We performed a case-control study comparing 131 cases of late-onset infection collected from 27 surgeons at 10 centers with 500 controls matched for date of surgery and surgeon. The criterion for the presence of infection was severe anterior chamber reaction occurring later than 4 weeks after surgery. An opaque bleb and positive culture results were not required for diagnosis. Risk factors were identified by univariate and multivariate logistic regression analyses. RESULTS: Some of the risk factors that were statistically significant in the multivariate model after adjusting for age, race, and sex were (1) performance of a full-thickness rather than a guarded procedure (risk ratio [RR], 13.1; 95% confidence interval [CI], 2.12-80.9), (2) filtration surgery performed without concurrent cataract surgery (RR, 2.25; 95% CI, 1.24-4.08), (3) use of mitomycin (RR, 2.48; 95% CI, 1.06-5.83), (4) intermittent use of antibiotics after surgery (RR, 2.10; 95% CI, 1.09-4.02), and (5) continuous use of antibiotics after surgery (RR, 5.94; 95% CI, 2.09-16.9). CONCLUSIONS: Eyes undergoing full-thickness procedures or filtration surgery without cataract extraction are at increased risk for late infection. Intraoperative mitomycin and episodic or continuous antibiotic use after the postoperative period are associated with an increased risk of infection.

Glaucoma patients' assessment of their visual function and quality of life.

PURPOSE: To determine how glaucoma patients with various degrees of vision loss rate their vision, and to determine if the Esterman binocular visual field test and other visual function tests correlate with those ratings. METHODS: Two hundred thirty-seven glaucoma patients evaluated their vision using 2 utility tests, the linear rating scale and the time trade-off test, and 2 quality-of-life instruments, the National Eye Institute Visual Function Questionnaire (VFQ) and the Short Form 36 (SF-36). Their results were compared to clinical tests of their vision and to persons with normal vision (n = 12) and blind persons (n = 12). RESULTS: On a scale of 0 (blind) to 100 (ideal), subjects with normal vision rated their vision higher (90 +/- 8.0) than did glaucoma subjects and suspects (75.7 +/- 17.6) and "blind" subjects (15.6 +/- 15.3), P = .001. Mean scores for the Esterman test were 89.7 +/- 13.4 for the glaucoma group. The Esterman test correlated moderately with the overall VFQ score (partial correlation coefficient [PCC] = 0.32, P = .001), but only weakly with the linear rating scale (PCC = 0.17, P = .02) and the time trade-off test (PCC = -0.16, P = .06). Correlation between the linear rating scale and the overall VFQ score was good (PCC = 0.56, P = .0001) and was moderate with several domains of the SF-36 (e.g., social function PCC = 0.32, P = .0001). CONCLUSIONS: Utility values that glaucoma patients assign to their vision do not correlate well with Esterman test results. A challenge for the future will be designing clinical tests that better correlate with patient perceptions.

Bleb reduction and bleb repair after trabeculectomy.

OBJECTIVE: To describe methods and outcomes for repair of bleb-related complications of trabeculectomy surgery. DESIGN: Retrospective, consecutive, noncomparative case series. PARTICIPANTS: Thirty-one persons having bleb revision by two surgeons at the Wilmer Institute from 1994 to the present. INTERVENTION: One of two types of revision surgery was performed: bleb reduction to decrease symptoms from large blebs or bleb repair to improve hypotony, using conjunctival rotation flap or free conjunctival autograft. MAIN OUTCOME MEASURES: Visual acuity, intraocular pressure (IOP), reported symptoms, complications, and number of glaucoma medications at the final visit. RESULTS: The mean time from trabeculectomy to bleb revision was 4.4 years. Bleb reduction was performed because of symptomatic, high blebs in 11 eyes of 11 persons. Bleb repair was performed to end bleb leakage in 13 eyes of 13 persons and to increase IOP in 8 eyes of 7 persons with hypotony. Median visual acuity improved from 20/50 before revision to 20/30 at most recent follow-up. Mean IOP increased after treatment from 7.7+/-4.9 to 12.4+/-4.0 mmHg (P < 0.001). Symptoms that caused the revision surgery were eliminated in all cases. None of these eyes has lost IOP control, none has required repeat trabeculectomy, and only 2 of the 32 (6%) require topical glaucoma medication. More than one revision procedure was required in 8 of 32 (25%) eyes. CONCLUSIONS: Surgical bleb revisions for complications after trabeculectomy surgery are safe and effective. Bleb reduction for large, symptomatic blebs or bleb repair for leaking blebs and hypotony did not lead to loss of IOP control.

Discordance of primary infantile glaucoma in monozygotic twins.

PURPOSE: To report a case of primary infantile glaucoma occurring in only one of two identical twins. METHODS: Case reports. RESULTS: Clinical features of bilateral primary infantile glaucoma in one of the two twins at age 16 months are described. Polymorphic DNA markers were used to establish identical twinship. CONCLUSION: Our finding suggests that nongenetic factors must be considered in determining the origin of primary infantile glaucoma.

The effect of paclitaxel powder on glaucoma filtration surgery in rabbits.

OBJECTIVE: The authors determine if the intraoperative placement of paclitaxel powder in the subconjunctival space improves the outcome of glaucoma filtration surgery in rabbits. METHODS: A posterior lip sclerectomy was performed in the right eye of 24 New Zealand white rabbits. Before the conjunctiva was fully sutured, 8 mg of mannitol powder alone, or 8 mg of mannitol powder containing either 10 micrograms or 250 micrograms of paclitaxel, was placed in the subconjunctival space of six eyes each in masked fashion. An additional six animals were treated with episcleral application of a sponge soaked in a solution of 0.5 mg/ml of mitomycin C (MMC) for 5 minutes before the sclerectomy was performed. Intraocular pressure and bleb size were measured until the operation had failed or until the 7 weeks of observation had concluded. RESULTS: Both paclitaxel powder and MMC solution improved the outcome of filtration surgery in this model as measured by magnitude of intraocular pressure (IOP) lowering and duration of surgical success. No toxic effect of either drug was observed, although endophthalmitis was observed in eight animals followed for more than 3 weeks. CONCLUSION: The introduction of paclitaxel into the subconjunctival space at the conclusion of filtration surgery has an effect comparable to intraoperative MMC.

Aqueous humor uric acid and ascorbic acid concentrations and outcome of trabeculectomy.

OBJECTIVE: To determine if there is an association between the surgical outcome of trabeculectomy and uric acid and ascorbic acid concentrations in the aqueous humor at the time of the procedure. PATIENTS, MATERIALS, AND METHODS: Aqueous humor samples were collected from the eyes of 169 of 249 adult patients who underwent trabeculectomy alone for any type of glaucoma between April 1989 and July 1995. Postoperatively, all medical records were reviewed and outcomes were classified as successful, unsuccessful, or indeterminate. The ascorbic acid and uric acid concentrations were determined in masked fashion by high-pressure liquid chromatography. Factors associated with surgical outcome were determined. RESULTS: Uric acid concentration was higher in unsuccessful eyes (mean+/-SD, 0.21+/-0.08 mmol/L, n=26) than in successful eyes (0.15+/-0.09 mmol/L, n=91, 95% confidence interval for difference, 0.02-0.10 mmol/L). Ascorbic acid levels were not significantly different in the eyes with unsuccessful (1129.9+/-601.9 micromol/L) and successful (1334.3+/-511.0 micromol/L) surgery (95% confidence interval for difference, -475.2 to 66.4 micromol/L, P=.13) surgery. Other factors associated with failure were previous surgery and surgery performed at the inferior limbus. A multiple polytomous logistic regression analysis was performed, after excluding the small number of operations performed at the inferior limbus. The odds ratio for failure increased by a factor of 1.68 for every 1-mmol/L increase in uric acid (95% confidence interval, 1.16-2.43, P=.006). CONCLUSIONS: Uric acid levels were higher at the time of surgery in eyes that had unsuccessful outcomes than in those with successful outcomes. No significant difference in ascorbic acid levels was detectable. A higher uric acid level in the aqueous humor is a risk factor for trabeculectomy failure and might be tested as a prognostic indicator [corrected].

The case for medical savings accounts.

The debate about health care reform has centered around managed care and its ramifications. Medical savings accounts (MSAs), on the other hand, have been relegated to the background of the congressional discussion of health care reform. Conservative Republicans have advocated MSAs, whereas they have been denigrated by many liberals. The Clinton administration has threatened to veto any legislation that includes MSA provisions. I believe that MSAs are in general poorly understood by physicians and deserve closer attention. This article will explain what MSAs are and how they work. The advantages of MSAs will be discussed and examples of MSAs in action will be provided.

Expression of carbonic anhydrase isozyme III in the ciliary processes and lens.

PURPOSE: To determine whether carbonic anhydrase isozyme (CA) III is expressed in the ciliary processes and lens. METHODS: Total RNA was isolated from rabbit ciliary epithelium and human ciliary processes and from the anterior lens of rabbit, cow, and human eyes. First-strand cDNA was synthesized, and the polymerase chain reaction (PCR) was performed using oligomer primers designed to amplify CA III sequences specifically. Selected PCR products were eluted from agarose gels, cloned, and sequenced. Northern blots were performed to confirm the presence of CA III in these tissues. RESULTS: Polymerase chain reaction products of the predicted size were generated from rabbit ciliary epithelium and from rabbit, bovine, and human lens. The sequence of the PCR product from human lens was identical to the published sequence of the corresponding region of the human CA III gene. The sequence of the PCR products from rabbit ciliary epithelium and bovine lens showed 88% and 97% identity, respectively, with the corresponding sequences for human CA III, suggesting that the PCR products corresponded to the rabbit and bovine orthologs. Northern blots confirmed the presence of CA III mRNA in the rabbit ciliary epithelium and in rabbit and bovine lens. CONCLUSIONS: mRNA for CA III is present in the intraocular tissues of rabbits, cows, and humans. The previous detection of CA III protein in the bovine lens is confirmed, and it extended to the lenses of other species, including humans. The detection of mRNA for CA III in the ciliary epithelium is new and suggests that the ciliary epithelium contains not only isozymes II and IV but isoenzyme III as well. Although the function of CA III in the eye is unknown, it may play a role in fluid transport and homeostasis.

Comparison of three tonometers for measuring intraocular pressure in rabbits.

PURPOSE: Rabbits are used commonly for the evaluation of drugs and surgery to lower intraocular pressure (IOP). The authors compared the accuracy and variability of three tonometers for measuring IOP in rabbits. METHODS: The anterior chamber of adult rabbits was cannulated with a 25-gauge needle connected to an elevated bottle of balanced salt solution. The bottle was raised and lowered to control IOP. A fluid-filled pressure transducer also was placed in the anterior chamber. Intraocular pressure was decreased in increments of 5 to 10 cm H2O from 50 to 0 mm Hg and was recorded with each of these instruments: the hand-held applanation tonometer, the Tono-pen XL, and the pneumatonometer. RESULTS: The Tono-pen XL and the hand-held applanation tonometer underestimated the IOP, whereas the pneumatonometer slightly overestimated IOP. Under close stopcock conditions, at IOPs between 3 and 30 mm Hg, the Tono-pen XL was as accurate as the pneumatonometer but had a smaller variance; the hand-held applanation tonometer had lower accuracy and higher variability. CONCLUSIONS: The Tono-pen XL is the tonometer of choice for measuring IOP in rabbits within the range of IOP 3 to 30 mm Hg. All tonometers were less accurate when the IOP was elevated markedly.

Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders.

BACKGROUND: Retinal ischemia induces intraocular neovascularization, which often leads to glaucoma, vitreous hemorrhage, and retinal detachment, presumably by stimulating the release of angiogenic molecules. Vascular endothelial growth factor (VEGF) is an endothelial-cell-specific angiogenic factor whose production is increased by hypoxia. METHODS: We measured the concentration of VEGF in 210 specimens of ocular fluid obtained from 164 patients undergoing intraocular surgery, using both radioimmuno-assays and radioreceptor assays. Vitreous proliferative potential was measured with in vitro assays of the growth of retinal endothelial cells and with VEGF-neutralizing antibody. RESULTS: VEGF was detected in 69 of 136 ocular-fluid samples from patients with diabetic retinopathy, 29 of 38 samples from patients with neovascularization of the iris, and 3 of 4 samples from patients with ischemic occlusion of the central retinal vein, as compared with 2 of 31 samples from patients with no neovascular disorders (P < 0.001, P < 0.001, and P = 0.006, respectively). The mean (+/- SD) VEGF concentration in 70 samples of ocular fluid from patients with active proliferative diabetic retinopathy (3.6 +/- 6.3 ng per milliliter) was higher than that in 25 samples from patients with nonproliferative diabetic retinopathy (0.1 +/- 0.1 ng per milliliter, P = 0.008), 41 samples from patients with quiescent proliferative diabetic retinopathy (0.2 +/- 0.6 ng per milliliter, P < 0.001), or 31 samples from nondiabetic patients (0.1 +/- 0.2 ng per milliliter, P = 0.003). Concentrations of VEGF in vitreous fluid (8.8 +/- 9.9 ng per milliliter) were higher than those in aqueous fluid (5.6 +/- 8.6 ng per milliliter, P = 0.033) in all 10 pairs of samples obtained simultaneously from the same patient; VEGF concentrations in vitreous fluid declined after successful laser photocoagulation. VEGF stimulated the growth of retinal endothelial cells in vitro, as did vitreous fluid containing measurable VEGF. Stimulation was inhibited by VEGF-neutralizing antibodies. CONCLUSIONS: Our data suggest that VEGF plays a major part in mediating active intraocular neovascularization in patients with ischemic retinal diseases, such as diabetic retinopathy and retinal-vein occlusion.

Pharmacokinetics of etoposide delivery by a bioerodible drug carrier implanted at glaucoma surgery.

PURPOSE: Pharmacological modulation of wound healing after glaucoma filtration surgery is of great clinical interest, but there are only limited data available on drug pharmacokinetics following glaucoma filtration surgery. Therefore we have studied the in vivo release and tissue distribution of etoposide (VP-16) delivered subconjunctivally by a bioerodible drug-carrier during filtration surgery in rabbits. METHODS: Disks composed of the polyanhydride 1,3-bis(p-carboxyphenoxy) propane and sebacic acid (PCPP:SA) in a weight ratio of 25:75 and containing 1 mg of 3H-etoposide were placed subconjunctivally during posterior lip sclerectomy in one eye of albino rabbits. Animals were euthanized at various times after surgery and etoposide concentrations in fluids and tissues were determined using liquid scintillation counting. RESULTS: Release of etoposide from the implant was nearly linear over time, at 30 ug/day, except for a burst between days 6 and 7. By the twelfth postoperative day, 92% of the etoposide had been released. Steady state levels averaged 89 ng/mg in the conjunctiva and sclera, 195 ng/ml in the vitreous, and 29 ng/ml in serum. Drug levels in the aqueous humor, other ocular tissues, and in the contralateral eye were negligible. CONCLUSIONS: The concentration of etoposide delivered by a polyanhydride controlled release device on the ocular surface is sufficient to reduce fibroblast proliferation for at least 12 days after filtration surgery.

Determination of protein concentration in aqueous humor.

SUMMARY: Accurate determination of protein concentration in the aqueous humor is important in the interpretation of experiments relevant to the pathogenesis and therapy of glaucoma. We made preliminary observations that the high concentration of ascorbic acid in aqueous humor might interfere with commonly used protein determination assays. Therefore, we tested the effect of ascorbic acid upon absorbance in the bicinchoninic acid (BCA), Lowry, and Bradford assays. Ascorbic acid and bovine serum albumin, alone and in combination, were added to BCA, Lowry, and Bradford reagents in 96-well plates. Absorbance was measured at 562 nm (BCA) and 590 nm (Lowry and Bradford). As little as 40 ng and 28 mug of ascorbic acid (typical aqueous humor concentration is 200-400 mug/ml) altered absorbance in the BCA and Lowry assays, respectively. The Bradford assay was not affected by ascorbic acid. Because of the high ascorbic acid and low protein concentration in aqueous humor, assays such as the BCA and Lowry, which are dependent upon oxidation-reduction reactions, must be used with caution. In most situations, the Bradford method is best for determination of aqueous humor protein concentration.

Glaucoma filtration surgery in nonhuman primates using taxol and etoposide in polyanhydride carriers.

PURPOSE: To determine the effect of taxol and etoposide, hydrophobic drugs with antifibrosis activity, on the outcome of filtration surgery in glaucomatous monkeys. METHODS: Elevated intraocular pressure was produced bilaterally in eight cynomolgus monkeys by laser treatment of the trabecular meshwork. Four animals subconjunctivally received a polyanhydride disk containing 1 mg etoposide at the time of posterior lip sclerectomy in one eye; the other eye received an identical disk without drug. Similarly, four animals received a disk containing 50 micrograms of taxol in one eye and a blank disk in the other. RESULTS: Eyes treated with taxol had lower intraocular pressures than control eyes from 20 days after surgery until death. Eyes with satisfactory filtration bleb appearance and patent fistulae on histologic examination had lower intraocular pressures. The intraocular pressure was lower and the duration of success longer in the etoposide-treated eyes (mean, 16 days) compared to that of the fellow eyes (mean, 10 days), but the difference was not statistically significant. CONCLUSIONS: Use of polyanhydride disks containing taxol, but not etoposide, had a marked beneficial effect on intraocular pressure and bleb appearance after experimental filtration surgery in monkeys. The difference between the two agents may result from the greater antiproliferative potency of taxol and its greater duration of release from the polymer.

Immunolocalization of TGF-beta 1, TGF-beta 2, and TGF-beta 3 in the anterior segment of the human eye.

PURPOSE: To determine the distribution of transforming growth factor type beta (TGF-beta) in the anterior segment of the human eye. This knowledge is important because TGF-beta may regulate various physiologic responses in the anterior segment by controlling cell proliferation and differentiation, angiogenesis, and extracellular matrix composition. METHODS: Immunohistochemical methods were used to localize the beta 1, beta 2, and beta 3 isoforms of TGF-beta in the anterior segment of the human eye. RESULTS: Eight of eight eyes (six eye bank specimens and two eyes enucleated because of choroidal melanoma) exhibited staining for at least one of the TGF-beta isoforms. TGF-beta 1 was found in superficial limbal epithelial cells (four of eight eyes) and in the stroma proximal to the ciliary processes (seven of eight eyes). TGF-beta 2 was found in superficial limbal epithelial cells (six of eight eyes), the conjunctival stroma (eight of eight eyes), in the ciliary processes (three of eight eyes), and in a diffuse distribution in the region of the radial and circular muscles of the ciliary body (eight of eight eyes). In addition, TGF-beta 2 was found in the stroma adjacent to the pigmented epithelium in the pars plana (eight of eight eyes). TGF-beta 3 was found in white blood cells in one of eight specimens; otherwise it was not found in the anterior segment. The corneal stroma, corneal endothelium, trabecular meshwork, iris, and ciliary epithelia did not exhibit immunoreactivity with the antibodies used in this study. CONCLUSION: TGF-beta 1 and TGF-beta 2 have a distinct and specific distribution in the anterior segment of the adult human eye.