Findings at this years ARVO meeting run the gamut from compliance and nutrional benefits to surgical success rates and the impact of gene variants on a patients likelihood to develop glaucoma.

 

ICEST Results

At this years ARVO, results from the International Collaborative Exfoliation Syndrome Treatment (ICEST) Study were published.2474/A149 The study examined treatment with latanoprost with pilocarpine vs. timolol vs. fixed-combination timolol/dorzolamide in eyes with exfoliation syndrome and elevated IOP. Researchers in New York, Chicago and Greece conducted this 12-year trial with 277 patients and randomized them to receive latanoprost/pilocarpine, timolol or timolol/dorzolamide. After 12 years of six-month follow-up, the researchers found that the group that underwent therapy with latanoprost and pilocarpine demonstrated lower IOP, improved outflow facility and decreased trabecular meshwork pigmentation. Also, say researchers, initial therapy to reduce aqueous outflow and disrupt exfoliation material dispersion by reducing movement of the pupil is preferable to reducing aqueous secretion.

 

Medications, Compliance and Nutrition

Over a six-month period, researchers in Mexico and California found that a fixed dose of timolol/brimonidine/dorzolamide more effectively reduced IOP than a fixed-combination of timolol/dorzolamide.2478/A153 In this multicenter, double-masked, randomized clinical trial, 112 patients with either open-angle glaucoma or ocular hypertension used one of the two drug formulations. At six months, mean IOP change from baseline to conclusion was significantly greater in the timolol/brimonidine/dorzolamide groupa difference of 9.90mm Hg 2.95mm Hgthan in the timolol/dorzolamide group, which demonstrated a difference of 6.8mm Hg 3.42mm Hg. And, researchers note that a fixed combination drug seems to improve patient compliance by reducing the total amount of drops per day. This new pharmaceutical combination agent may soon become available in the United States.

Does education actually have an impact on patients compliance? Absolutely, say researchers in Greece, North Carolina and Maryland.2477/A152 In this one-year study, 107 patients were randomized into a group that received intensive adherence education for the year or a group that received the same quantity of education about eye care (not compliance- or glaucoma-specific). All participants drops featured an electronic dosing counter. IOP and rate of adherence were compared at one, three, six, nine and 12 months. Researchers found that adherence was markedly better in the first group at all time points, with a difference of more than 10% between the groups. This study reminds us of the importance of thorough patient education in the ongoing treatment of glaucoma.

Vitamins may aid in the management of glaucoma, say researchers in Los Angeles.2071 In this study, 52 patients with primary open-angle glaucoma (POAG) and 19 control subjects underwent ophthalmic evaluation, dietary intake assessment and serum level measurement.

Researchers found that, though there were no statistically significant differences in dietary intake, serum levels of alpha-carotene and lutein were significantly lower in the glaucoma group than in the control group38g/L vs. 106g/L for alpha-carotene and 111g/L vs. 189g/L for lutein. So, vitamins may play a role in the management of POAG, if properly understood.

 

CCT, Oxygen and Thin Corneas: Higher Risk? Researchers in St. Louis, Mo., set out to measure the levels of oxygen and ascorbic acid in the eyes of patients undergoing intraocular surgery.1671 What they found was an inverse relation between CCT and oxygen in the eye that may account for the increased risk of glaucoma in persons with thinner corneas. Researchers sampled the oxygen in the anterior chamber (AC), mid-AC and near the corneal endothelium. In certain eyes, oxygen was sampled near the posterior chamber and anterior lens surface as well. Ascorbic acid levels were calculated through colorimetric analysis and aqueous humor sample assessment. In control eyes (undergoing their first procedure), oxygen levels were highest near the cornea and descending toward the lens surface and posterior chamber. In eyes undergoing cataract extraction, there was significantly more oxygen in the posterior chamber and the AC angle. The inverse relationship between CCT and oxygen may account for increased risk of glaucoma in patients with thinner corneas, a previously unexplained association. These measurements, which define oxygen gradients in the eye, suggest that the vitreous and the natural lens both play a role in regulating oxygen distribution and metabolism in the eyenot to mention, the importance of these structures in the development of glaucoma, say researchers.

Corneal Thickness

Measurement of central corneal thickness (CCT) may not suffice when differentiating between healthy and glaucomatous eyes, found researchers in West Virginia and California.4911/A308 Over the course of one year, researchers used ultrasound pachymetry five times per day to measure CCT. When examining the daily averages, researchers found that the CCT of 26% of normal eyes and 20% of eyes with POAG varied by more than 30m between visits. And, researchers note that this variation could be due to true variation or measurement inconsistency, concluding therefore that CCT may vary over time and one reading may not suffice to characterize true corneal thickness.

But, how stable is CCT in patients with high-risk ocular hypertension or early glaucoma? Not very, say researchers in Iowa City, Ia.4896/A293 Researchers set out to determine what factors influence CCT in this patient cohort by examining 176 patients for the influence of age, gender and treatment history. There are significant gender and medication effects on CCT. Keep in mind that eyes with a history of ocular hypotensive medication show a significantly greater rate of corneal thinning.

 

Genetic Influence

Much research of late has focused on identification of genetic predisposition toward glaucoma.

Researchers in Durham, N.C., set out to identify links between additional gene variants and POAG, and found that a gene linked to Alzheimers disease may be related to POAG as well.881/A467 Dynamin-binding protein is associated with late-onset Alzheimers disease in Belgian and Japanese populations; however, when it is combined with coding variant C1413W, the protein results in an increased association with POAG in a white population.

 Variants in the gene LOXL1 contribute to the formation of abnormal fibers characteristic of pseudoexfoliation glaucoma, say researchers in Germany and Oregon.863/A449 Postmortem analysis of 15 eyes with pseudoexfoliation glaucoma and 15 control eyes revealed significant upregulation of elastic fiber components in eyes with LOXL1. And, double-immunolabeling demonstrated co-localization of the fiber components and LOXL1. Researchers note that this gene could be targeted in possible future therapies.

But, some of the polymorphisms of LOXL1 do not influence IOP, CCT or cup-to-disc ratio, say researchers in Greece and Texas.867/A453 In this clinical and genetic study, 600 villagers from one Greek town were enrolled (376 villagers were linked in one 11-generation line). Two variants of LOXL1 were mapped and found to not affect CCT, IOP or cup-to-disc ratio. In one subset, however, there was a significant association between one variation, rs3825942, and CCT in cases of POAG. Otherwise, the LOXL1 variants did not play a significant role, but the study population was limited.

Lastly, single nucleotide polymorphisms (SNPs) within LOXL1 may play a critical role in the pathogenesis of pigment dispersion syndrome (PDS) and pigmentary glaucoma (PG), say researchers in Italy.878/A464 In a cohort of 73 unrelated patients who had either PDS or PG, researchers found a strong association between the combined LOXL1 SNPs and PDS or PG.

 

Blood Flow

Studies at this years meeting definitively confirm the significant importance of blood flow in the glaucoma process.

Reduced blood flow in the optic nerve head is associated with an increased degree of visual field defect and to the glaucomatous disease process, found researchers in Austria and Germany.5868/A206 Examination of 103 patients with POAG revealed that optic nerve head blood flow was negatively correlated with cup-to-disc ratio and positively correlated to retina nerve fiber layer (RNFL) cross section.

Researchers in Israel, New York and Germany found that central retinal artery blood flow is positively correlated with mean RNFL thickness.5805/A143 In 61 patients with POAG, RNFL thickness was found to follow the ISNT rule and blood flow velocities were measured in the ophthalmic, central retinal and nasal and temporal short posterior ciliary arteries. Increases in blood flow positively correlated with increased thickness in the superior region of the RNFL.

 

Progression

Wait and see is a viable approach to attaining accurate disease progression measurement, say researchers in London.1669 Rather than perform three visual field tests over the period of two years (the current suggested method of estimating rapid progression), researchers created a simulation of patients and control subjects and tested them every four months, or three times at baseline and three times at two years. And, they recorded the time until detection. In the group of patients tested every four months, 83% were diagnosed correctly with rapid progression by two years. But, 95% were identified in the wait and see group. Also, rate of loss was better estimated in this group, though identification was slightly quicker (a difference of 3.1 months) in the four-month group. Rapid progression may be more reliably predicted with fewer false positives and one fewer visual field if we wait and see.

Also, visual field loss may indicate areas of imminent disc hemorrhage, found researchers in New York, N.Y.6197 In this retrospective study, quick localized visual field loss predicted hemorrhage location in 80% of cases, and after hemorrhage detection, the indicating visual field sector demonstrated the fastest progression of the entire field in 92% of cases. So, say researchers, disc hemorrhage should be viewed not only as a risk factor for future progression but also as evidence of past field loss and rim structural collapse.

Ages Effects on the Cornea and Glaucoma Risk How does aging affect corneal biomechanical properties, such as corneal hysteresis, CCT and corneal resistance factornot to mention, IOP? Researchers in La Jolla, Calif., measured the eyes of 95 patients at various ages to answer this question.5221 They found that hysteresis decreases with age, corneal stiffness increases with age, and that neither CCT nor corneal resistance factor are significantly affected by aging alone. IOP also tended to increase with age. Researchers note that these findings are a step in the right direction, but that further research must be done to understand additional age-related risk factors for glaucoma.

Researchers in California and Brazil compared the rates of change of retinal nerve fiber layer (RNFL) and neuroretinal rim area in glaucomatous patients to see which would be an effective indicator of progression.2252/A194 In this study of 199 eyes, 14% showed progression; the RNFL and rim area were measured in these over 3.6 years. RNFL thinning progressed by 0.53m per year, while rim thinning demonstrated only a 0.003m annual change. So, the RNFL is a stronger indicator of progression, say researchers.

 

Surgery

How successful is the modern trabeculectomy in POAG when using the safe surgery system, ask researchers in Portsmouth, United Kingdom.168/A268 The answer: The safe surgery system is effective in the management of POAG when paired with close monitoring and prompt intervention, as needed.

Researchers followed patients who had POAG and no history of previous glaucoma surgery. Of the 98 eyes followed, 95 surpassed the criteria for qualified successof these, 91 achieved complete success. Two patients procedures failed due to conservative postoperative management, and one patient required a redo. Ten patients developed cataract, but subsequent phacoemulsification and IOL insertion were uncomplicated.

Researchers in New York, N.Y., measured the IOP-lowering effects of selective laser trabeculoplasty (SLT) in patients who could not control their IOP with maximum therapy and found that SLT can reduce IOP by as much as 22% without severe side effects or complications.158/A258 With one preoperative drop of brimonidine, researchers treated 360 of the trabecular meshwork. No anti-inflammatory medications were used postoperatively. Patients were evaluated on days 1, 30, 90 and 180, and until day 90, patients were required to continue with their current glaucoma medication regimen. Among the 30 eyes involved, mean IOP decreased from 19.6mm Hg to 15.2mm Hg at 30 days, 15.8mm Hg 3.5mm Hg at 90 days, and 17.4mm Hg 2.8mm Hg at 180 days. Visual acuity remained unchanged over the follow-up period. Mean number of IOP-lowering medications required dropped from 2.4 to 1.9not a very significant change, say researchers. But, no serious complications occurred.

Not only can SLT affect IOP, but also trabecular outflow facility (TOF), say researchers in London.154/A254 In patients with POAG or ocular hypertension (OHT), one eye received either 180 or 360 of treatment with SLT. Fellow eyes that did not require treatment were used as controls. Over the course of one month, eyes in the 180 group demonstrated IOP reduction from 24.4mm Hg 4.1mm Hg to 19.0mm Hg 5.2mm Hg and TOF increase from an average of 0.08 to 0.11. Results in the 360 group were similar. Overall, SLT treatment, either 180 or 360, reduced IOP by 29% and increased TOF by 38%.

Another procedure that can safely lower IOP in POAG patients is canaloplasty, say researchers in Indianapolis, Ind.458/A241 This retrospective analysis included 30 eyes, 26 of which underwent canaloplasty combined with cataract surgery, while four underwent only canaloplasty. Through an assessment of IOP, necessary medications, visual acuity and postoperative complications, researchers determined that the procedure lessened patients dependency on IOP medications. At six months post-op, IOP was lowered to 13.2mm Hg 3.7mm Hg from 19.4mm Hg 8.8mm Hg. The number of glaucoma medications also decreasedfrom 2.0 preoperatively to 0.20.6 afterward. Postoperative complications included hyphema (16 eyes), subconjunctival hemorrhage (9 eyes) and transient bleb (14 eyes).

Is it better to perform only phacoemulsification (phaco) or to perform it in tandem with endocyclophotocoagulation (ECP)? Researchers in Gainesville, Fla., say that, surprisingly, phaco alone results in a stronger decrease in IOP.446/A229 In this retrospective review, patients IOP was measured post-op at one day, one week, one month and five months. In the ECP/phaco group, researchers found a drop in IOP from 16.7mm Hg 5.0mm Hg to 15.0mm Hg 4.4mm Hg. But, in the phaco-only group, IOP decreased from 15.0mm Hg 4.4mm Hg to 14.1mm Hg 4.3mm Hg. At every follow-up, patients in the phaco-only group demonstrated a lower IOP than those in the ECP/phaco group, a somewhat surprising conclusion.

Both treatment methods equally reduced patients dependency on medications, though, reducing it to about 2.0a statistically insignificant difference.

For the text of each abstract, referenced here by presentation number, please go to www.arvo.org.