A comparison of cup-to-disc ratio estimates by fundus biomicroscopy and stereoscopic optic disc photography in the Tema Eye Survey.

PurposeTo determine if there are systematic differences in cup-to-disc ratio (CDR) grading using fundus biomicroscopy compared to stereoscopic disc photograph reading.MethodsThe vertical cup-to-disc ratio (VCDR) and horizontal cup-to-disc ratio (HCDR) of 2200 eyes (testing set) were graded by glaucoma subspecialists through fundus biomicroscopy and by a reading center using stereoscopic disc photos. For validation, the glaucoma experts also estimated VCDR and HCDR using stereoscopic disc photos in a subset of 505 eyes that they had assessed biomicroscopically. Agreement between grading methods was assessed with Bland-Altman plots.ResultsIn both sets, photo reading tended to yield small CDRs marginally larger, but read large CDRs marginally smaller than fundus biomicroscopy. The mean differences in VCDR and HCDR were 0.006±0.18 and 0.05±0.18 (testing set), and -0.053±0.23 and -0.028±0.21 (validation set), respectively. The limits of agreement were ~0.4, which is twice as large as the cutoff of clinically significant CDR difference between methods. CDR estimates differed by 0.2 or more in 33.8-48.7% between methods.ConclusionsThe differences in CDR estimates between fundus biomicroscopy and stereoscopic optic disc photo reading showed a wide variation, and reached clinically significance threshold in a large proportion of patients, suggesting a poor agreement. Thus, glaucoma should be monitored by comparing baseline and subsequent CDR estimates using the same method rather than comparing photographs to fundus biomicroscopy.

The effect of medical therapy on IOP control in Ghana.

BACKGROUND: To investigate IOP control following twelve months of continuous medical therapy in Ghana. METHODS: This retrospective case series included 163 glaucoma patients diagnosed at a referral eye center between 1996 and 2006. Information collected included age, gender, IOP at presentation, six months and one year post treatment and types of anti-glaucoma medications prescribed. Optimal IOP control was defined according to results from the Advanced Glaucoma Intervention Study (AGIS), which demonstrated arrest of visual field progression in patients with IOP < 18 mmHg at all visitations: Level 1 (post-treatment IOP ≤ 21 mmHg); Level 2 (≤ 18 mmHg) and level 3 (≤ 16 mmHg). The principal outcome measure was the achievement of IOP <18 mmHg at six months and twelve month visitations. RESULTS: One hundred sixty three patients were analyzed. These included 68 males (41.7%) and 95 females (58.3%). The mean age was 57±16 (median 59 years; range 7 - 95 years). There was no significant difference in age (p=0.35) or mean IOP (p=0.08) between genders. The mean pre-treated IOP of 31.9±8.9 mmHg significantly decreased to 21.3±6.6 mmHg at 6 months (p=0.001), with 57.4% of eyes at Level 1 IOP control, 25.3% at Level 2 and 15.4% at Level 3 and decreased further at 12 months to 20.7±6.9 mmHg (p=0.48) with 69.7% of eyes at Level 1, 34.4% at Level 2, and 12.4% at Level 3. CONCLUSIONS: Current medical regimen is insufficient to reduce IOP to target levels as defined in the Advanced Glaucoma Intervention Study.

Health literacy and vision-related quality of life.

BACKGROUND: Non-visual factors influence a person's vision-related quality of life (VRQoL). The purpose of this study was to assess the relationship between health literacy and VRQoL in glaucoma patients. METHODS: One hundred and ninety-five subjects with open-angle glaucoma participated in a cross-sectional patient survey and chart review. Subjects were administered a test of health literacy, an assessment of physical and mental well-being, and an assessment of VRQoL, the National Eye Institute 25-Item Visual Function Questionnaire (VFQ-25). Charts were reviewed for visual acuity and visual field results. RESULTS: In univariate analyses, older age (p<0.001), non-White race (p<0.001), worse visual acuity (p<0.001), worse visual field scores (p<0.001), lower level of education (p<0.001), worse health literacy (p<0.001) and worse score on the mental health component of the SF-12 (p = 0.005) were associated with worse VFQ-25 scores. In multivariate analyses, only older age was associated with worse total VFQ-25 scores (p<0.001), although the association between health literacy and the VFQ subscale of dependency remained significant (p = 0.04). CONCLUSIONS: Individuals with a lower health literacy do not appear to have a worse overall VRQoL compared with those with a higher literacy, but worse health literacy is associated with increased dependency.

Longitudinal changes in central corneal thickness and their relation to glaucoma status: an 8 year follow up study.

AIMS: To determine if central corneal thickness (CCT) changes over time and if this change relates to glaucoma progression. METHODS: 39 patients (64 eyes) with open angle glaucoma, ocular hypertension, glaucoma suspect status, or a normal eye examination were examined at two visits. CCT, age, race, sex, family history of glaucoma, presence of diabetes and systemic hypertension, diagnosis, visual acuity, spherical equivalent, intraocular pressure, vertical and horizontal cup to disc ratios, number of glaucoma medications prescribed, Advanced Glaucoma Intervention Study (AGIS) score and mean deviation of Humphrey visual fields, and interventions required were recorded. Statistical analysis used the Wilcoxon signed ranks test, linear regression, and analysis of variance. RESULTS: Between the two visits (mean 8.2 years apart), mean CCT decreased by 17 mum in right eyes (p<0.002) and by 23 mum in left eyes (p<0.001). This decrease was greater in right eyes of patients with primary open angle glaucoma than in normals (p = 0.041). There was no significant association between change in CCT and other examination parameters. Change in CCT was not associated with topical carbonic anhydrase inhibitor use. CONCLUSION: In this longitudinal study, CCT decreased over time, but this may not be related to glaucoma progression.

Prevalence of myocilin mutations in adults with primary open-angle glaucoma in Ghana, West Africa.

PURPOSE: Investigators have noted that primary open-angle glaucoma (POAG) in West Africa has an earlier age of onset and appears to be more clinically severe than in the United States and Europe. Primary open-angle glaucoma patients with mutations in myocilin have a similar phenotype. Therefore, we investigated the role of mutations in myocilin in patients with POAG in a West African population. MATERIALS AND METHODS: Patients seen at the Emmanuel Eye Clinic in Accra, Ghana, were recruited for this study. Informed consent was obtained from all study patients. Glaucoma specialists from the sponsoring institution (PC, LWH, or RRA) ascertained all POAG and control patients. Age-matched unaffected controls were obtained in patients with an IOP < 22 mm Hg and normal-appearing optic nerves. PCR amplification of each of the three myocilin exons was performed. Denaturing high-performance liquid chromatography (Transgenomics Corp.) was used to detect allelic differences and samples demonstrating a mobility shift were sequenced in both directions. RESULTS: Ninety unrelated affecteds with POAG and 76 control patients were recruited. Four individuals with severe POAG were found to have novel missense mutations in exon 3. Two exhibit an Asp380Asn mutation and two an Arg342Lys mutation. These changes were not detected in 152 ethnically matched control chromosomes. Fourteen affected individuals and eight controls exhibit a translationally silent polymorphism in codon 325 (Thr325Thr). CONCLUSIONS: A total of 4.4% of patients with POAG have novel disease-associated mutations in myocilin. Mutations in myocilin appear to play a limited role in the pathogenesis of POAG in this region of West Africa.

The Acp26Aa seminal fluid protein is a modulator of early egg hatchability in Drosophila melanogaster.

Drosophila melanogaster male accessory gland proteins (Acps) that are transferred in the ejaculate with sperm mediate post-mating competition for fertilizations between males. The actions of Acps include effects on oviposition and ovulation, receptivity and sperm storage. Two Acps that modulate egg production are Acp26Aa (ovulin) and Acp70A (the sex peptide). Acp26Aa acts specifically on the process of ovulation (the release of mature eggs from the ovaries), which is initiated 1.5 h after mating. In contrast, sperm storage can take as long as 6-9 h to complete. Initial ovulations after matings by virgin females will therefore occur before all sperm are fully stored and the extra eggs initially laid as a result of Acp26Aa transfer are expected to be inefficiently fertilized. Acp26Aa-mediated release of existing eggs should not cause a significant energetic cost or lead to a decrease in female lifespan assuming, as seems likely, that the energetic cost of egg laying comes from de novo egg synthesis (oogenesis) rather than from ovulation. We tested these predictions using Acp26Aa(1) mutant males that lack Acp26Aa but are normal for other Acps and Acp26Aa(2) males that transfer a truncated but fully functional Acp26Aa protein. Females mating with Acp26Aa(2) (truncation) males that received functional Acp26Aa produced significantly more eggs following their first matings than did mates of Acp26Aa(1) (null) males. However, as predicted above, these extra eggs, which were laid as a result of Acp26Aa transfer to virgin females, showed significantly lower egg hatchability. Control experiments indicated that this lower hatchability was due to lower rates of fertilization at early post-mating times. There was no drop in egg hatchability in subsequent non-virgin matings. In addition, as predicted above, females that did or did not receive Acp26Aa did not differ in survival, lifetime fecundity or lifetime progeny, indicating that Acp26Aa transfer does not represent a significant energetic cost for females and does not contribute to the survival cost of mating. Acp26Aa appears to remove a block to oogenesis by causing the clearing out of existing mature eggs and, thus, indirectly allowing oogenesis to be initiated immediately after mating. The results show that subtle processes coordinate the stimulation of egg production and sperm storage in mating pairs.

Antithrombin III, a serpin family protease inhibitor, is a major heparin binding protein in porcine aqueous humor.

Our hypothesis is that the proteins in aqueous humor may be involved in the regulation of outflow facility through the trabecular meshwork and uveoscleral meshwork. In this study, we analyzed the profile of heparin-binding proteins present in porcine aqueous humor to identify and characterize secretory proteins with a binding affinity for heparin. A single step involving heparin-sepharose affinity chromatography of porcine aqueous humor yielded a approximately 60 kDa protein as the major heparin-binding species. This protein was specifically eluted from the column by heparin. The N-terminal sequence and immunological cross reactivity of this protein confirmed its identity as antithrombin III. Aqueous humor from different species, as well as cells from human trabecular meshwork, Schlemm's canal, and lens epithelium, contained detectable amounts of antithrombin III. Based on its known anticoagulative function in endothelial cells and effects on the production of prostacyclin, it is reasonable to speculate that antithrombin III present in aqueous humor might influence the physiology of the trabecular and uveoscleral meshwork and thereby regulate intraocular pressure.

Excisional bleb revision to correct overfiltration or leakage.

OBJECTIVES: To evaluate the effectiveness of excisional revision of filtering blebs for hypotony or leakage when more conservative measures have failed. PATIENTS AND METHODS: Retrospective review of all patients who underwent excisional revision of a filtering bleb for hypotony (intraocular pressure [IOP] < 5 mm Hg) or leakage during a 3 year period. The revision consisted of excision of the avascular bleb, mobilization of the surrounding conjunctiva, and suturing of the conjunctiva at the limbus. RESULTS: Sixteen patients were included in the study. The average age was 66.3 +/- 14.8 years (range, 39-83). Revision followed trabeculectomy in 11 cases, combined phacoemulsification-trabeculectomy in three cases, and inadvertent blebs in two cases. Five cases had bleb leaks without hypotony, four cases had hypotony alone, and seven cases had both hypotony and a bleb leak. Average follow-up after bleb revision was 25 +/- 11 months (range, 9-43). Average IOP increased from 3.8 +/- 5.6 mm Hg (range, 0-22) to 11.9 +/- 4.1 mm Hg (range, 3-18), with an average of 1.1 +/- 1.1 medication (range, 0-3). The IOP at the last visit was < 15 mm Hg in all but two patients, with 10 of the 16 patients requiring medications. At the last follow-up examination, visual acuity had improved > or = two lines in nine patients and was reduced two lines in one patient. Five patients had early postoperative limbal wound leaks; resuturing was required in one case. CONCLUSIONS: Excisional bleb revision is an effective technique to correct hypotony or leakage after filtering surgery when other methods have failed. Intraocular pressure control is often maintained with the use of medications.

A clinical comparison of transscleral cyclophotocoagulation with neodymium: YAG and semiconductor diode lasers.

PURPOSE: To compare the efficacy of transscleral cyclophotocoagulation using a neodymium: YAG (Nd:YAG) or semiconductor diode laser in controlling intraocular pressure in patients with refractory glaucoma. METHODS: In a prospective study, 95 eyes of 91 patients with refractory glaucoma randomly received Nd:YAG or diode cyclophotocoagulation. Patients were followed for a mean of 10.4 months (10.42 +/- 3.16, mean +/- SD). We compared available data preoperatively and at 1 week, 1 month, 6 months, and 12 months postoperatively. Data analyzed were corrected visual acuity, intraocular pressure, and the type of glaucoma. RESULTS: There was a statistically significant decrease in intraocular pressure after both Nd:YAG and diode cyclophotocoagulation at each time period. However, there were no significant differences in postoperative intraocular pressure or visual acuity change between Nd:YAG and diode procedures. CONCLUSIONS: Compared with the Nd:YAG laser for transscleral cyclophotocoagulation, the diode laser has technological advantages including portability, durability, and smaller size, while providing equivalent postoperative intraocular pressure and visual acuity change.

Use of latanoprost in the treatment of glaucoma associated with Sturge-Weber syndrome.

PURPOSE: To determine if latanoprost reduces intraocular pressure in eyes with glaucoma associated with Sturge-Weber syndrome. METHODS: We conducted a prospective study in which eyes with uncontrolled intraocular pressure associated with Sturge-Weber syndrome were treated with latanoprost 0.005% once daily. All eyes were already receiving at least two other antiglaucoma medications. Intraocular pressure was measured at baseline and after treatment for at least 1 month. All intraocular pressure measurements were taken within 24 hours of drug instillation. RESULTS: Six eyes of six patients received latanoprost. Two (28%) of the six eyes demonstrated an intraocular pressure decrease that averaged 8.8 mm Hg. These two responders had juvenile onset glaucoma, whereas the four nonresponders had congenital onset glaucoma. CONCLUSIONS: Latanoprost may significantly reduce intraocular pressure in selected patients with glaucoma associated with Sturge-Weber syndrome.

Adult-onset primary open angle glaucoma does not localize to chromosome 2cen-q13 in North American families.

Glaucoma is one of the leading causes of irreversible blindness in the world and is characterized by elevated intraocular pressure, optic nerve atrophy, and progressive visual field loss. Primary open angle glaucoma (POAG) is the most common subtype of glaucoma in the United States. Recently, Stoilova and coworkers [Genomics 1996;36:142-150] identified a locus for POAG on chromosome 2 (2cen-q13) in families primarily located in the United Kingdom. We examined families with POAG identified within the US for linkage to the 2cen-q13 locus. A total of 18 families with POAG were used in the analysis. Of 77 family members, 46 were classified as affected and 31 were either glaucoma suspects or considered normal. Eight highly polymorphic and informative markers flanking and distributed throughout the region were used. Parametric lod score analysis was performed using both a dominant and recessive low penetrance or 'affecteds-only' model. Multipoint affected sibpair exclusion mapping was also performed. Lod score (both models) and sibpair analysis excluded linkage of the POAG phenotype to the 2cen-q13 region in these families. These data suggest that the chromosome 2cen-q13 locus does not explain a substantial amount of genetic variation in familial POAG.

Laser energy reaching the posterior pole during transscleral cyclophotocoagulation.

OBJECTIVE: To measure scattered laser energy reaching the posterior pole during transscleral cyclophotocoagulation. METHODS: Transscleral cyclophotocoagulation was performed on 4 cadaver eyes with Nd:YAG noncontact, Nd:YAG contact, and diode contact lasers. Energy was measured with a photodiode through a 7-mm trephined hole in the posterior pole. Average percentage power, average power, and average energy transmission were calculated. American Conference of Governmental Industrial Hygienists (ACGIH) guidelines were used to calculate allowable energy exposures for each laser. RESULTS: All 3 lasers transmitted 3% to 5% of the power to the posterior pole. The average energy transmission was 240 to 260 mJ for all lasers. The contact lasers had an average power transmission of 120 mW. The noncontact Nd:YAG laser, with shorter pulse duration, had an average power transmission of 13,000 mW, significantly greater than that of the other lasers. The ACGIH guidelines for allowable energy exposures were 93 mJ for the noncontact Nd:YAG laser, 1300 mJ for the contact Nd:YAG laser, and 440 mJ for the contact diode laser. CONCLUSIONS: Three percent to 5% of laser power delivered during cyclophotocoagulation reaches the posterior pole. Exposure energies may approach or exceed ACGIH guidelines. The clinical significance of these findings remains to be shown.

Results of trabeculectomy with 0.3 mg/ml mitomycin C titrating exposure times based on risk factors for failure.

PURPOSE: To examine the efficacy of trabeculectomy with mitomycin C 0.3 mg/ml using titrated exposure times. METHODS: A retrospective chart review of consecutive patients undergoing trabeculectomy in an academic referral glaucoma clinic was performed. All patients received trabeculectomies performed by one surgeon (M.B.S.). The study included 57 eyes of 57 patients using mitomycin C with exposure times titrated from one to five minutes based on risk factors for trabeculectomy failure. Surgical success was defined as a final intraocular pressure (IOP) of less than 21 mmHg with or without medications or a 25% reduction in IOP if preoperative IOP was 21 mmHg or less. Patients requiring repeat trabeculectomies were considered failures regardless of their final IOP. Patients receiving different mitomycin C exposure times were compared but statistical analysis was not used because these subgroups were not randomized. RESULTS: An overall surgical success rate of 84.2% was achieved at a mean follow-up of 11.9 months. The surgical success rate and percentage IOP reduction was similar between exposure time subgroups. Hypotonous maculopathy observed in three patients (5.3%). All cases of hypotonous maculopathy was occurred in the lower-risk patients receiving one to three minute exposure times to mitomycin C. CONCLUSIONS: We believe mitomycin C should be used sparingly if at all in patients at lower risk for trabeculectomy failure. This concentration of mitomycin C with four to five minute exposure times appears to be efficacious for patients with multiple risk factors for trabeculectomy failure.

Genetically targeted cell disruption in Caenorhabditis elegans.

The elimination of identified cells is a powerful tool for investigating development and system function. Here we report on genetically mediated cell disruption effected by the toxic Caenorhabditis elegans mec-4(d) allele. We found that ectopic expression of mec-4(d) in the nematode causes dysfunction of a wide range of nerve, muscle, and hypodermal cells. mec-4(d)-mediated toxicity is dependent on the activity of a second gene, mec-6, rendering cell disruption conditionally dependent on genetic background. We describe a set of mec-4(d) vectors that facilitate construction of cell-specific disruption reagents and note that genetic cell disruption can be used for functional analyses of specific neurons or neuronal classes, for confirmation of neuronal circuitry, for generation of nematode populations lacking defined classes of functional cells, and for genetic screens. We suggest that mec-4(d) and/or related genes may be effective general tools for cell inactivation that could be used toward similar purposes in higher organisms.

Central corneal thickness in normal, glaucomatous, and ocular hypertensive eyes.

OBJECTIVE: To determine the relationship between central corneal thickness (CCT) and applanation intraocular pressure (IOP) in normal, glaucomatous, and ocular hypertensive eyes. METHODS: One hundred nine subjects (184 eyes) were studied. Forty-eight patients (74 eyes) had glaucoma, 28 patients (51 eyes) had ocular hypertension, and 33 patients (59 eyes) were normal. Intraocular pressure as measured by applanation tonometry, refractive status, CCT, and axial length were measured for all subjects. RESULTS: The CCT (mean +/- SD) of eyes with ocular hypertension was significantly greater (0.606 +/- 0.041 mm) than that of glaucomatous eyes (0.554 +/- 0.022 mm) (P < .001) or of normal controls (0.561 +/- 0.026 mm) (P < .001). There was no significant difference in CCT between normal and glaucomatous eyes (P = .40). The axial length (mean +/- SD) of eyes with ocular hypertension (23.54 +/- 1.34 mm) was not different compared with glaucomatous eyes (23.93 +/- 0.96 mm) (P = .13) or normal eyes (23.62 +/- 1.21 mm) (P = .83). There was no significant difference between the axial length for glaucomatous eyes compared with normal eyes (P = .18). Those eyes with glaucoma being treated with topical dorzolamide hydrochloride had a significantly increased CCT (0.560 +/- 0.025 mm) compared with those eyes with glaucoma not being treated with dorzolamide (0.551 +/- 0.20 mm) (P = .02). CONCLUSIONS: The mean CCT is increased in eyes with ocular hypertension when compared with normal or glaucomatous eyes, which confirms the findings of other investigators. Increased CCT may give an artificially high IOP measurement by applanation tonometry. The CCT must be considered when developing a treatment approach for patients with ocular hypertension.

Efficacy of autologous blood injection for treating overfiltering or leaking blebs after glaucoma surgery.

PURPOSE: To evaluate the efficacy of autologous blood injections for treating overfiltering or leaking blebs after glaucoma surgery. METHOD: Retrospective review of ten eyes of ten patients who received intrableb autologous blood injections for hypotonous maculopathy. RESULTS: After intrableb blood injection, average intraocular pressure increased from 4.3 mm Hg to 6.4 mm Hg, and average visual acuity improved from 20/88 to 20/77. These results, however, were not statistically significant. CONCLUSION: Our results with autologous blood injection are less favorable than those of previous reports, although further study with a larger case series is needed.

Mating and hormonal triggers regulate accessory gland gene expression in male Drosophila.

Drosophila melanogaster males transfer accessory gland proteins, as part of their seminal fluid, to females during each mating. Since accessory gland proteins are important for male reproductive success, it is important that the male replenish the proteins he transferred during mating. Previous studies had shown that mating induces the resynthesis of accessory gland proteins, but since mating includes a set of stereotyped behavior patterns as well as the act of copulation, it was not known which aspect of the mating process induces accessory gland protein synthesis. By exposing males to females whose ovipositors had been sealed shut, we have shown that resynthesis of accessory gland proteins occurs only when seminal fluid is transferred to females. By applying juvenile hormone or 20-hydroxyecdysone topically to the cuticle of male flies, we showed that these hormones can act in vivo to stimulate the synthesis of accessory gland proteins to levels similar to those observed after mating.