Rajul S. Parikh

Five year risk of progression of primary angle closure suspects to primary angle closure: a population based study

Aim: To report progression of primary angle closure suspects (PACS) to primary angle closure (PAC) at the 5 year follow up of a population based sample. Methods: 82 of 118 PACS who could be contacted and 110 randomly selected normals from a population based survey in 1995 were invited for a follow up examination in 2000. Progression to PAC was based on the development of raised IOP or synechiae in a PACS. Results: 50 of the 82 PACS contacted were examined. 11 (22%; 95% CI 9.8 to 34.2) developed PAC (seven synechial and four appositional); all were bilateral PACS. Two of 50 people previously diagnosed as PACS were reclassified as normal. One person among the 110 normals progressed to PAC. The relative risk of progression among PACS was 24 (95% CI 3.2 to 182.4). There was no significant difference in axial length, anterior chamber depth, or lens thickness between those who progressed and those who did not. None of the patients developed optic disc or field damage attributable to angle closure. One angle closure suspect was diagnosed to have normotensive glaucoma. Conclusion: In this population based study of PACS the 5 year incidence of PAC was 22%; none developed functional damage. Bilateral PACS was a clinical risk factor for progression.

Diagnostic capability of Macular parameters of Stratus OCT 3 in detection of early glaucoma

Aim To report the diagnostic capability of Stratus OCT macular parameters in early glaucoma. Material and methods In a cross-sectional observational study, two groups of subjects (early glaucoma and normals) who satisfied the inclusion and exclusion criteria were recruited. The diagnosis of early glaucoma was based on a glaucomatous appearance of the optic disc correlating with visual-field defects (fulfilling at least two of three Anderson and Patella criteria, with a mean deviation better than or equal to −6 dB. All patients underwent a complete ophthalmic evaluation including visual-field examination (24−2/30−2 SITA standard programme) and imaging with Stratus OCT 3. The macular thickness map in Stratus OCT includes the fovea, inner macula and outer macula, with diameters of 1, 3 and 6 mm, a total of nine sectors. Sensitivity, specificity, area under the receiving operating characteristic curve (AUROC) and likelihood ratio were calculated for volume and thickness parameters in these nine sectors. Results 56 eyes (56 patients) with early glaucoma and 75 eyes (75 normals) were analysed. Only two parameters, the outer inferior average volume (p = 0.003) and the outer inferior average thickness (p = 0.002), were statistically significantly lower in the glaucoma group. Outer inferior average volume had a “best combination” of sensitivity and specificity (56% and 79% respectively). Both outer inferior average volume and thickness parameters yielded the best AUROCs of 0.66. Conclusions Outer inferior macular thickness and volume parameters in early glaucoma are significantly different from normals. The moderate sensitivity and specificity suggest that the role of macular parameters in the diagnosis of early glaucoma is limited.

The LOXL1 Gene Variations Are Not Associated with Primary Open-Angle and Primary Angle-Closure Glaucomas

PURPOSE Glaucoma is a complex disease involving multiple genetic factors. Recently, single nucleotide polymorphisms (SNPs) in the LOXL1 gene have been implicated in exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) but not in the primary glaucomas. This study was conducted to determine the possible involvement of these SNPs in cases of primary open-angle glaucoma (POAG) and primary angle-closure glaucoma (PACG). METHODS The three associated SNPs of LOXL1 (rs1048661, rs3825942, and rs2165241) were screened in 208 unrelated and clinically well-characterized glaucoma cases comprising patients with POAG (n = 112) or PACG (n = 96) along with 105 ethnically matched normal control subjects from Indian populations. Subjects with exfoliative material on the lens and radial pigmentation in the periphery of the lens that could be earlier signs of XFS were excluded. These SNPs were screened by resequencing and further confirmed by PCR-based restriction digestions. Haplotypes were generated with the three SNPs in cases and control subjects, and linkage disequilibrium (LD) and haplotype analysis were performed with the Haploview software, which uses the EM (expectation-maximization) algorithm. RESULTS The SNPs of LOXL1 did not exhibit any significant association with POAG or PACG, unlike previous studies from Icelandic, Swedish, U.S., and Australian populations with XFS/XFG. Haplotypes generated with these intragenic SNPs did not indicate any significant risk with POAG or PACG phenotypes. The risk haplotype G-G in XFS/XFG in other populations was present in 46% of the normal control subjects in the present cohort. CONCLUSIONS The results from the present study do not indicate the involvement of the LOXL1 SNPs in POAG and PACG.

Clear lens extraction in angle closure glaucoma.

Purpose of review Clear lens extraction is being advocated for primary angle closure disease (PACD). It is important that this advocacy should be based on a sound, peer-reviewed evidence base. This review attempts to establish the extent of that evidence and provide some management guidelines. Recent findings There are only three reports that incorporate clear lens extraction (CLE) for angle closure: numbers are sparse and none compare modern phacoemulsification to alternative treatments for primary angle closure glaucoma or provide enough detail to guide clinical decisions. A Cochrane review in 2006 found that there was no evidence to support lens extraction as treatment for primary angle closure glaucoma (PACG). More recent randomized controlled trials have provided support for cataract extraction – although not specifically for CLE – as treatment for part of the spectrum of PACD. A recent review has attempted to provide guidelines for application of CLE in PACG by extrapolating from this evidence. Summary There are currently no randomized controlled trials supporting the use of CLE as treatment for PACG. A benefit from the procedure is biologically plausible and extrapolation from existing randomized trials to a few specific situations may be possible. Any potential benefit must be carefully weighed against the risks of intervention.

The Transcription Factor Gene FOXC1 Exhibits a Limited Role in Primary Congenital Glaucoma

PURPOSE Primary congenital glaucoma (PCG) is an autosomal recessive disorder that has been linked to CYP1B1 mutations. This study was conducted to explore the role of FOXC1, which is involved in anterior segment dysgenesis, in PCG. METHODS An earlier screening for CYP1B1 in a clinically well-characterized PCG cohort (n = 301) revealed cases that were either homozygous (n = 73), compound heterozygous (n = 18), or heterozygous (n = 41) for the mutant allele, whereas the remaining (n = 169) did not harbor any mutation. Hence, FOXC1 was screened in 210 PCG cases who were either heterozygous (n = 41) or did not harbor any CYP1B1 mutation (n = 169), along with ethnically matched normal control subjects (n = 157) by resequencing the entire coding region. RESULTS Two heterozygous missense (H128R and C135Y) and three frame shift mutations (g.1086delC, g.1155del9bp, and g.1947dup25bp) were observed in FOXC1 in 5 (2.38%) of 210 cases. The missense mutations had a de novo origin in two sporadic cases, whereas the FOXC1 deletions were seen in two cases that were also heterozygous for the CYP1B1 allele (R368H). The parents of the proband with g.1086delC were heterozygous for either the FOXC1 or CYP1B1 alleles. The unaffected mother of the proband with the g.1155del9bp was heterozygous for both the FOXC1 and CYP1B1 alleles; the father harbored only the FOXC1 allele. Familial segregation of the g.1947dup25bp could not be performed because of the unavailability of DNA from one parent. Except for the g.1155del9bp (0.95% normal chromosomes), all the other variations were absent in the control subjects. CONCLUSIONS The present study indicates a limited role of FOXC1 in PCG pathogenesis.

Likelihood ratios: Clinical application in day-to-day practice

In this article we provide an introduction to the use of likelihood ratios in clinical ophthalmology. Likelihood ratios permit the best use of clinical test results to establish diagnoses for the individual patient. Examples and step-by-step calculations demonstrate the estimation of pretest probability, pretest odds, and calculation of posttest odds and posttest probability using likelihood ratios. The benefits and limitations of this approach are discussed.

There is insufficient evidence to recommend lens extraction as a treatment for primary open-angle glaucoma: an evidence-based perspective.

Cataract extraction in primary open‐angle glaucoma has not been thought to provide a clinically useful or predictable decrease in IOP. This concept has now been challenged, with the opposite belief being promulgated: namely, that lens exchange should be considered as treatment for glaucoma. This revelation could bring a significant change in the glaucoma treatment paradigm.

Practical approach to medical management of glaucoma

Primary open angle glaucoma (POAG) is usually a chronic, slowly progressive disease. At present, all resources are directed towards reduction of intraocular pressure (IOP), the only known causal and treatable risk factor for glaucoma, and medical management is frequently the first choice in most cases. With the introduction of innovative tools for early diagnosis and newer medications for treatment, decision-making in diagnosis and treatment of glaucoma has become more complex. The philosophy of glaucoma management is to preserve the visual function and quality of life (QOL) of the individual with minimum effects on QOL in terms of cost, side effects, treatment regime, follow-up schedules as well as socioeconomic burden. Our aim should be not to treat just the IOP, optic disc or visual field, but to treat the patient as a whole so as to provide maximum benefit with minimal side effects. In this article, we describe the scientific approach to medical management, mainly of POAG.

Primary angle closure glaucoma: a developing world perspective

Primary angle closure glaucoma (PACG) is estimated to affect a significant proportion of the population worldwide. Of those affected, the majority reside in developing countries. In the developing world, more than 80% of the people afflicted with glaucoma are unaware that they have the disease, and visual impairment from PACG is more severe than from primary open‐angle glaucoma. Considering the paucity of resources and competing opportunity costs, it is imperative that the developing world extrapolates current literature and exiting data sensibly, and develops cost‐effective strategies for the detection and management of angle closure glaucoma. The number needed to treat (NNT) was used to extrapolate the trials for an individual patient. To extrapolate to the overall population (where applicable) the authors used the population attributable risk percentage (PAR%). For individual patient care, treatment of a primary angle closure suspect (PACS) has an NNT of 6 over 5 years to prevent one patient progressing to primary angle closure (PAC). The NNT for PAC to prevent PACG over 5 years is 5. The ‘effective’ PAR% for PACS is 56.4% and the ‘effective’ PAR% for PAC is 65%. This suggests both PACS and PAC are important health burdens but because of the absence of a good screening test and the opportunity costs involved, population‐based screening will probably be unfeasible in developing countries.

Applying the recent clinical trials on primary open angle glaucoma: the developing world perspective.

Abstract:Recent clinical trials have provided scientific guidelines for the treatment of ocular hypertension and primary open angle glaucoma. The developing world need to apply these trials in a sensible and cost effective manner. The number needed to treat (NNT) attempts to tailor treatment to the individual patient. The NNT for the average ocular hypertensive is 20. Those with intraocular pressure ≥26 mm Hg have an NNT of 6. Restricting treatment to those with lower central corneal thickness and or high cup disc ratios can further lower NNT and make treatment more cost effective. The NNT for the average patient with early POAG is 5. Targeting those at higher risk for progression, (bilateral POAG, higher IOP and or pseudo-exfoliation) can further reduce NNT. As far as the modality of treatment is concerned, provided quality can be ensured, collaborative initial glaucoma treatment study (CIGTS) could be interpreted to justify primary surgery in the developing world context.Population attributable risk percentage (PAR), a measure that reflects the public health importance of a disease was used to extrapolate results to the overall population. Ocular hypertension has an “effective” PAR of 8.5%, a value not considered high enough to warrant public health intervention. POAG had an “effective” PAR of 16%, perhaps high enough to be considered a public health problem and justify inclusion as a target disease in the Vision 2020 program. However the logistics and opportunity costs of diagnosis and treatment would probably prevent inclusion of POAG in public health budgets of most developing countries.