Mark S. Juzych

Adjunctive Mitomycin C in Primary Trabeculectomy in Phakic Eyes

PURPOSE The addition of antiproliferative agents, most recently mitomycin C, has improved the outcome of glaucoma filtering surgery in eyes with a high risk of surgical failure. We conducted the present study to determine whether adjunctive mitomycin C would increase the success rate of primary trabeculectomies in phakic eyes. METHODS Thirty-three eyes of 33 consecutive patients with phakic primary open-angle glaucoma, who were predominantly black (24 black and nine white), who underwent primary trabeculectomy with adjunctive subconjunctival mitomycin C (0.5 mg/ml for three minutes) were compared with a demographically similar historical control group of 30 eyes of 30 consecutive patients (20 black and ten white) with phakic primary open-angle glaucoma, who had undergone primary trabeculectomy without an adjunctive antifibrotic agent. RESULTS Although the mean preoperative intraocular pressures were similar in both groups (29.0 +/- 6.4 mm Hg in the mitomycin C group and 29.5 +/- 10.0 mm Hg in the control group, P = .61), the mean postoperative intraocular pressure at each follow-up period was significantly lower in the mitomycin C group than in the control group (10.3 +/- 7.1 vs 14.5 +/- 5.1 mm Hg at six months, P = .02; 10.5 +/- 4.9 vs 14.5 +/- 4.4 mm Hg at 12 months, P = .01; and 10.0 +/- 3.1 vs 17.2 +/- 3.0 mm Hg at 18 months, P = .004, respectively). The mean number of postoperative medications was also significantly lower in the mitomycin C group (0.2 +/- 0.4 vs 1.1 +/- 1.4 medications at six months, P = .007; 0.3 +/- 0.4 vs 0.9 +/- 1.1 medications at 12 months, P = .04; and 0.3 +/- 0.5 vs 1.7 +/- 1.2 medications at 18 months, P = .01, respectively). However, the mitomycin C group had a significantly higher incidence of prolonged hypotony (intraocular pressure less than 6 mm Hg) compared with the control group (15% vs 0% at nine months, P = .05). Younger age was associated with a higher incidence of persistent hypotony. CONCLUSIONS Adjunctive subconjunctival mitomycin C (0.5 mg/ml for a three-minute exposure) in primary trabeculectomies of phakic eyes, while increasing the success rate by decreasing intraocular pressure and postoperative medications, is associated with a higher incidence of prolonged hypotony.

Cyclophotocoagulation: A report by the American Academy of Ophthalmology

OBJECTIVE This document describes cyclophotocoagulation procedures for glaucoma and examines the evidence to answer key questions about patient selection, and efficacy of transscleral and endoscopic techniques. METHODS A literature search conducted for the years 1968 to 2000 retrieved 130 citations. The author reviewed 34 of these articles and selected 19 for the panel methodologist to review and rate according to the strength of evidence. A Level I rating is assigned to properly conducted, well-designed, randomized clinical trials; a Level II rating is assigned to well-designed cohort and case-control studies; and a Level III rating is assigned to case series and poorly designed prospective and retrospective studies, including case-control studies. RESULTS The predominant problem with all studies on cyclophotocoagulation is the lack of a uniform definition of success, which makes comparisons difficult. One randomized controlled trial (Level I evidence) compared the efficacy of transscleral cyclophotocoagulation with noncontact Nd:YAG and semiconductor diode laser. It found no significant difference between the two, although a significant problem was the variability allowed with laser parameters. Most of the literature consists of noncomparative case series that provide evidence that is limited and often not convincing. CONCLUSION Cyclophotocoagulation is indicated for patients with refractory glaucoma who have failed trabeculectomy or tube shunt procedures, patients with minimal useful vision and elevated intraocular pressure, and patients who have no visual potential and need pain relief (based on Level III evidence). It may be useful for patients whose general medical condition precludes invasive surgery or who refuse more aggressive surgery (i.e., filter or tube). It is also useful in emergent situations, such as the acute onset of neovascular glaucoma. There is insufficient evidence to definitively compare the relative efficacy of the cyclophotocoagulation procedures for glaucoma. It is the panels opinion, however, that semiconductor diode systems appear to possess the best combination of effectiveness (based on Level III evidence), portability, expense, and ease of use at this time.

Automated perimetry: A report by the American academy of ophthalmology

OBJECTIVE The purpose of this document is to summarize and evaluate the effectiveness of new automated perimetry tests and algorithms in diagnosing glaucoma and detecting disease progression. METHODS A literature search on automated perimetry retrieved over 300 citations from 1994 to 2001, of which 71 were selected as relevant to this assessment. The quality of the evidence obtained from these studies was assessed by the methodologist. RESULTS The four automated perimetry techniques described in this assessment are short wavelength automated perimetry (SWAP), frequency doubling technology perimetry (FDT), high-pass resolution perimetry (HPRP), and motion automated perimetry (MAP). The algorithms described are Swedish interactive threshold algorithm (SITA) and SITA fast. With the exception of SWAP, these techniques and algorithms reduce testing time and inconsistent patient performance when compared with conventional full threshold testing. CONCLUSIONS Short wavelength automated perimetry detected visual field loss earlier than standard threshold automated perimetry, with a sensitivity and specificity of about 88% and 92% respectively. However, it is a lengthy, demanding test, is sensitive to media opacities, and has a greater magnitude of long-term fluctuation compared with standard threshold automated perimetry, which make it difficult to assess disease progression accurately. When compared to standard threshold automated perimetry, FDT perimetry showed sensitivity and specificity greater than 97% for detecting moderate and advanced glaucoma, and sensitivity of 85% and specificity of 90% for early glaucoma. As FDT perimetry has a short testing time and is resistant to blur and pupil size, it may be a useful screening tool. In a longitudinal study, high-pass resolution perimetry was more effective than standard threshold automated perimetry in monitoring progressive glaucomatous loss, detecting progression at a median of 12 months earlier in 54% of patients studied. Motion automated perimetry demonstrated usefulness in detecting early glaucomatous visual loss in a longitudinal study. Studies on SITA demonstrated greater sensitivity and reproducibility and less intertest variability when compared to standard full threshold testing and a 50% reduction in testing times. A study comparing standard full threshold, SITA, and SITA fast found a sensitivity of 95% for the first two techniques and 93% for SITA fast. Long-term follow-up studies are needed to assess the ability of these techniques to detect progression of glaucoma over time.

Corneal Endothelial Cell Counts After Molteno Implantation

Implantation of a Molteno drainage shunt has been shown to be effective in advanced glaucoma. Foreign substances within the anterior chamber have been known to cause progressive endothelial cell loss. We undertook a study to evaluate the endothelial effects of an indwelling Molteno drainage shunt. Nineteen patients who underwent uneventful implantation of a Molteno drainage shunt for advanced aphakic or pseudophakic glaucoma were followed up. Serial endothelial cell counts were obtained in a masked fashion. During follow-up periods ranging from 5.4 to 25.7 months, endothelial cell loss averaged two cells per square millimeter per postoperative month with a 95% confidence interval of positive seven cells to negative ten cells per square millimeter per postoperative month. No clinically significant progressive trend in endothelial cell loss was seen in patients undergoing uncomplicated Molteno drainage procedures. Larger sample sizes with longer follow-up will be necessary to establish whether a Molteno drainage shunt causes clinically remarkable endothelial cell loss.

Primary Glaucoma Triple Procedure with or without Adjunctive Mitomycin: Prognostic Factors for Filtration Failure

PURPOSE The prerequisite for selective use of adjunctive mitomycin C (MMC) in primary glaucoma triple procedure (PGTP) is a better understanding of the prognostic factors. Therefore, the authors carried out the current study on the outcome of PGTP with and without adjunctive MMC to determine the prognostic factors for filtration failure of PGTP. METHODS The study patients consisted of 174 consecutive primary open-angle glaucoma (POAG) patients undergoing PGTP. They were assigned randomly to either no adjunctive MMC (93 eyes of 93 patients) or adjunctive subconjunctival MMC (81 eyes of 81 patients) during the PGTP. After surgery, the patients were examined at regular intervals for visual acuity, intraocular pressure (IOP) control, medical therapy requirements, and complications. Filtration failure was determined according to two different criteria: (1) a less stringent set of criteria (criterion I) and (2) a more stringent set of criteria (criterion II). RESULTS There were no statistically significant differences between the groups with and without adjunctive MMC with respect to postoperative IOP, number of medications, and visual acuity outcome during mean follow-up (+/- standard deviation) of 25.1 +/- 5.5 months (P > 0.05 for each). However, there were prognostic factors for filtration failure in the control group but not in the MMC group. Black race, diabetes mellitus, preoperative IOP greater than or equal to 20 mmHg, and number of preoperative medications greater than two were found to be significant prognostic factors for filtration failure by criterion I. Black race, preoperative IOP greater than or equal to 20 mmHg and number of preoperative medications greater than 1 were significant prognostic factors for filtration failure by criterion II. CONCLUSION There was no statistically significant difference in the overall outcome of PGTP between control and MMC groups of nonselected patients with primary open-angle glaucoma. Black race, diabetes mellitus (by criterion I only), preoperative IOP greater than or equal to 20 mmHg, and number of preoperative medications greater than 2 (by criterion I) or greater than 1 (by criterion II) were found to be significant independent prognostic factors for filtration failure of PGTP without adjunctive MMC but no with adjunctive MMC. The use of adjunctive subconjunctival MMC in PGTP may have to be selective, primarily in those patients with primary open-angle glaucoma with one or more of the prognostic factors for filtration failure.

Pattern of Publication of Ophthalmic Abstracts in Peer-reviewed Journals

Presentation of research work at scientific meetings and professional societies is an important first step toward effective scientific communication of research results. To determine the current publication patterns of abstracts, a computerized MEDLINE literature search was performed on 175 randomly selected ophthalmic clinical and basic science abstracts published in conjunction with two ophthalmic national meetings. This search revealed that 105 abstracts (60%) led to full-length articles in peer-reviewed journals within 50 to 56 months of the meeting date. A median interval of 13 months occurred from date of abstract publication to acceptance of the corresponding article. Most articles appeared within 3 years of abstract presentation. Sixty-four percent (48 of 75) of the posters and free papers presented at the annual meeting of the American Academy of Ophthalmology in November 1984 led to full-length articles, as did 57% (57 of 100) of the abstracts presented at the annual meeting of the Association for Research in Vision and Ophthalmology in May 1985. These findings emphasize the preliminary nature of abstracts. The fact that nearly 60% of abstracts are published reflects favorably on the review process of both meetings.

Limbus-based vs fornix-based conjunctival flap in combined glaucoma and cataract surgery with adjunctive mitomycin C

PURPOSE To determine the efficacy and safety of limbus-based vs fornix-based conjunctival flaps in patients with primary open-angle glaucoma undergoing trabeculectomy combined with phacoemulsification and intraocular lens implantation with adjunctive subconjunctival mitomycin C. METHODS In a prospective study, 69 eyes of 69 patients with primary open-angle glaucoma, visually symptomatic cataracts, and no previous incisional ocular surgery were randomly assigned to limbus-based and fornix-based conjunctival flap groups. All patients received trabeculectomy combined with phacoemulsification and posterior chamber lens implantation with 1-minute (0.5 mg/ ml) application of subconjunctival mitomycin C. RESULTS The mean intraocular pressures were significantly (P < .05) lower on significantly (P < .05) fewer medications postoperatively at 1 week, 1 month, 3, 6, 9, 12, and 15 to 18 months, and at last follow-up in both groups than they had been preoperatively. However, there were no significant (P > .05) differences in postoperative mean intraocular pressure, mean number of medications, and visual acuity between the two groups at any time interval. Hypotony with wound leak was significantly (P = .019) higher in the limbus-based group. Other postoperative complications were not significantly (P > .05) different between the two groups. CONCLUSIONS There was no notable difference in glaucoma control or visual outcome between limbus-based and fornix-based conjunctival flaps in primary trabeculectomy combined with phacoemulsification and lens implantation with adjunctive subconjunctival mitomycin C. The fornix-based flap was as safe as, if not safer than, the limbus-based flap in the glaucoma triple procedure with adjunctive subconjunctival mitomycin C.

Primary glaucoma triple procedure in patients with primary open-angle glaucoma: The effect of mitomycin C in patients with and without prognostic factors for filtration failure

PURPOSE To investigate the effect of adjunctive mitomycin C on primary glaucoma triple procedure in patients with primary open-angle glaucoma with and without one or more of the prognostic factors for filtration failure of primary glaucoma triple procedure. Those factors include being of African-American race, having a preoperative intraocular pressure of 20 mm Hg or more on maximum tolerated medications, and being on two or more medications preoperatively. METHODS Study patients consisted of 197 consecutive patients with primary open-angle glaucoma who were randomly assigned to receive either no adjunctive mitomycin C (101 eyes of 101 patients) or to receive adjunctive subconjunctival mitomycin C (96 eyes of 96 patients) during the primary glaucoma triple procedure. Kaplan-Meier survival analysis comparisons were made between respective subgroups with and without prognostic indicators for filtration failures using a relatively stringent set of criteria for filtration success of primary glaucoma triple procedure. RESULTS There was no statistically significant (P = .117) difference in filtration success of primary glaucoma triple procedure between the control and mitomycin C groups. Adjunctive mitomycin C significantly (P < .05) improved the filtration outcome of the primary glaucoma triple procedure in the subgroups with each of the three prognostic factors for filtration failure of primary glaucoma triple procedure. On the other hand, in the subgroups without the prognostic factors, adjunctive mitomycin C did not significantly (P > .05) change the filtration outcome of the primary glaucoma triple procedure. CONCLUSION These findings establish the basis for selective use of mitomycin C in patients with primary open-angle glaucoma undergoing primary glaucoma triple procedure.

Adjunctive Subconjunctival Mitomycin C in Glaucoma Triple Procedure

PURPOSE To evaluate the potential benefit of adjunctive subconjunctival mitomycin in patients with primary open-angle glaucoma undergoing primary trabeculectomy combined with phacoemulsification and intraocular lens implantation. METHODS Seventy-eight eyes of 78 patients with primary open-angle glaucoma with visually symptomatic cataracts and no previous incisional surgery were randomized to receive either no mitomycin C or a subconjunctival application of 1-, 3-, or 5-minute mitomycin C (0.5 mg/ml). RESULTS Follow-up (mean +/- standard deviation) was 21.0 +/- 7.7 months. The mean postoperative intraocular pressures were significantly lower with significantly less medications than the preoperative values at each follow-up time (1, 3, 6, 9, 12, 15 months, and last follow-up) for all groups (P < 0.05 for each). However, there was no significant difference at each follow-up time in intraocular pressure, medications, or best-corrected visual acuity among the four groups or between the control and the total mitomycin C group. CONCLUSION Adjunctive subconjunctival mitomycin C did not further improve the final intraocular pressure outcome of the primary trabeculectomy combined with phacoemulsification and intraocular lens implantation in patients with primary open-angle glaucoma. Future studies will determine the appropriate role, if any, for adjunctive mitomycin C in selected primary glaucoma triple procedures.

Zika virus infects cells lining the blood-retinal barrier and causes chorioretinal atrophy in mouse eyes

Zika virus (ZIKV) is an important pathogen that causes not only neurologic, but also ocular, abnormalities. Thus, it is imperative that models to study ZIKV pathogenesis in the eye are developed to identify potential targets for interventions. Here, we studied ZIKV interactions with human retinal cells and evaluated ZIKVs pathobiology in mouse eyes. We showed that cells lining the blood-retinal barrier (BRB), the retinal endothelium, and retinal pigment epithelium (RPE) were highly permissive and susceptible to ZIKV-induced cell death. Direct inoculation of ZIKV in eyes of adult C57BL/6 and IFN-stimulated gene 15 (ISG15) KO mice caused chorioretinal atrophy with RPE mottling, a common ocular manifestation of congenital ZIKV infection in humans. This response was associated with induced expression of multiple inflammatory and antiviral (IFNs) response genes in the infected mouse retina. Interestingly, ISG15 KO eyes exhibited severe chorioretinitis, which coincided with increased retinal cell death and higher ZIKV replication. Collectively, our study provides the first evidence to our knowledge that ZIKV causes retinal lesions and infects the cells lining the BRB and that ISG15 plays a role in retinal innate defense against ZIKV infection. Our mouse model can be used to study mechanisms underlying ZIKV-induced chorioretinitis and to gauge ocular antiviral therapies.