Primary canaliculitis: clinical features, microbiological profile, and management outcome.

PURPOSE: To describe the demographic profile, clinical presentation, microbiological profile, and management outcome of primary canaliculitis. METHODS: Single-center, retrospective, interventional case series. Clinical records of all patients diagnosed with primary canaliculitis and treated at the Department of Ophthalmic Plastic Surgery, LV Prasad Eye Institute, Hyderabad, India, between 1987 and 2010 were reviewed. Retrospective data analysis included demographic profile, clinical presentation, microbiological profile, and management outcomes. The management outcome was further analyzed regarding conservative medical treatment alone, versus punctoplasty with canalicular curettage. RESULTS: Of the 74 patients, 40 (54%) were women. Mean age at presentation was 48 years. Right eye was involved in 38 (51%) patients, left eye in 34 (46%) patients, and both eyes in 2 (3%) patients. The mean delay in diagnosis was 10 months. Lower canaliculus was involved in 48 (65%) patients, upper canaliculus in 17 (23%) patients, and both canaliculi in 9 (12%) patients. The most common presenting symptom was epiphora, noted in 63 (85%) patients, and the most common clinical sign was thickening of canalicular portion of eyelid seen in 53 (72%) patients. Microbiological workup was available in 54 patients, of whom 49 (91%) yielded positive results. The most common isolate was staphylococcus species in 19 (39%) patients. Conservative medical therapy (punctal dilatation, canalicular expression, and topical antibiotics) resulted in resolution in 35 of 51 (69%) patients, whereas punctoplasty with canalicular curettage resulted in resolution in all 39 (100%) patients. Of the 74 patients, 57 (70%) resolved completely with single intervention, 14 (19%) with 2 interventions, 6 (8%) with 3 interventions, and 2 (3%) with 4 interventions. Recurrence was noted in 2 (3%) patients that subsequently resolved with treatment. CONCLUSION: Primary canaliculitis is predominantly a unilateral disease with a significant delay in diagnosis. The microbiological profile of canaliculitis is evolving, with staphylococcus species emerging as the most common pathogen. Although conservative medical therapy is beneficial, punctoplasty with canalicular curettage combined with topical antibiotic therapy is the gold standard treatment for canaliculitis.

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.

Glaucoma-associated CYP1B1 mutations share similar haplotype backgrounds in POAG and PACG phenotypes.

PURPOSE: To understand the involvement of the CYP1B1 gene in cases of primary open-angle (POAG) and primary angle-closure (PACG) glaucomas and obtain the haplotype background of these mutations. METHODS: The entire coding region of CYP1B1 was screened by resequencing in 224 unrelated cases of POAG (n = 134) and PACG (n = 90) and 200 ethnically matched normal control subjects from Indian populations. Six intragenic single nucleotide polymorphisms (SNPs) in CYP1B1 (-13T>C, R48G, A119S, V432L, D449D, and N453S) were used to generate haplotype data for the cases and controls and linkage disequilibrium (LD) and haplotype analysis were performed with Haploview software, which uses the EM (expectation-maximization) algorithm. RESULTS: The frequency of CYP1B1 mutations was higher among POAG (18.6%; 95% CI, 12.9-26.1) than PACG (11.1%; 95% CI, 6.1-19.3) cases. There was a marked allelic heterogeneity, and the Arg368His was the most prevalent mutation across both the phenotypes. The spectrum of CYP1B1 mutations was largely similar across different POAG populations. Haplotypes generated with intragenic SNPs indicated the C-C-G-G-T-A to be a risk haplotype associated with CYP1B1 mutations in POAG (P = 0.006) and PACG (P = 0.043), similar to that observed in cases of primary congenital glaucoma worldwide. CONCLUSIONS: The results demonstrate an involvement of CYP1B1 in a proportion of POAG and PACG cases that should be explored further. The similar haplotype background of these mutations is indicative of their common origin across multiple glaucoma phenotypes.

Recurrent uveitis and pigment dispersion in an eye with in-the-bag acrylic foldable intraocular lens.

Phacoemulsification with in-the-bag intraocular lens (IOL) implantation is the standard procedure for cataract surgery. Pigment dispersion and uveitis can result when an IOL is placed in the sulcus. We report a case of a 64-year-old woman, with pigmentary glaucoma, who developed recurrent uveitis following uneventful cataract surgery and an in-the-bag hydrophobic acrylic IOL implant. Recurrent uveitis did not subside despite use of topical steroids over 3 months. Dilated examination revealed capsulophimosis with anterior dislocation of the IOL haptic. The mechanical trauma to the iris due to the displaced haptic was implicated as the cause of recurrent uveitis, which completely resolved after capsular excision and IOL repositioning. This case illustrates a rare cause of recurrent uveitis due to IOL haptic dislocation following severe capsulophimosis.

Gln48His is the prevalent myocilin mutation in primary open angle and primary congenital glaucoma phenotypes in India.

PURPOSE: Myocilin gene defects have been originally implicated in primary open angle glaucoma (POAG). Based on multiple reports for the occurrence of Gln48His mutation (c.144G>T; HGMD accession number CM023962) among Indian POAG patients, we wanted to estimate the prevalence of this mutation in primary open angle and primary congenital glaucoma (PCG) in India and assess its role in the causation of the disease. METHODS: Two hundred cases each of POAG and PCG were screened for the Gln48His mutation by RFLP (AccI) analysis of the PCR amplicons followed by confirmation of the c.144G>T change by direct sequencing. RESULTS: The Gln48His mutation was detected in 9 different glaucoma patients (four POAG and five PCG). While all four POAG cases were heterozygous, among PCG cases, four were heterozygous and one exhibited homozygous genotype for the mutation. One each of POAG and PCG patients was detected to be heterozygous for CYP1B1 mutation (c.1656C>T, Pro437Leu) and (c.1449G>A, Arg368His), respectively. None of the 300 ethnically matched normal controls contained either the MYOC or CYP1B1 mutation(s). CONCLUSIONS: The myocilin mutation, Gln48His, represents an allelic condition involving a spectrum of glaucoma phenotypes in Indian populations, and could be a potential risk factor towards disease predisposition among patients of Indian origin. The study also highlights the role of MYOC as a candidate in different glaucoma subtypes that needs to be investigated further.

Evaluation of Optineurin as a candidate gene in Indian patients with primary open angle glaucoma.

PURPOSE: To evaluate the role of the optineurin gene (OPTN) in Indian primary open angle glaucoma (POAG) patients from different parts of the country. METHODS: Two hundred patients with POAG and 200 ethnically matched normal controls were recruited from various parts of India for the study. The entire coding region of OPTN along with the intron-exon boundaries were screened by PCR and single strand conformation polymorphism (SSCP) followed by direct sequencing. A rapid screening method was developed for some of the observed variants by denaturing high performance liquid chromatography (dHPLC). Four variants were also confirmed by digesting the amplicon with appropriate restriction enzymes. RESULTS: Seven nucleotide changes were observed in OPTN of which one was a putative mutation in exon 16 (Arg545Gln) that was observed in six POAG patients and not in the controls (p<0.05). The remaining variants comprised four single nucleotide polymorphisms (SNPs) in the coding region (Thr34Thr, Met98Lys, Arg149Arg, and Asn303Lys) and two in intron 6 (879-10G>A and 879-5C>T). But frequencies of the minor allele were not significantly different among the patients and controls. The Met98Lys variant that was identified to be a potential risk factor for NTG and POAG in some Asian populations and also for modulating IOP in Caucasian populations, did not exhibit any significant association to the disease phenotype. CONCLUSIONS: Despite a putative mutation (Arg545Gln) in some patients, the present study does not suggest a significant involvement of OPTN in POAG patients of Indian origin.

Variations in NTF4, VAV2, and VAV3 genes are not involved with primary open-angle and primary angle-closure glaucomas in an indian population.

PURPOSE: Recently, the neurotrophin-4 (NTF4), VAV2 and VAV3 genes have been implicated in primary open-angle glaucoma (POAG) in the European and Japanese populations, respectively. This study was conducted to determine their involvement in an Indian population with POAG and primary angle-closure glaucoma (PACG). METHODS: The entire NTF4 gene and the POAG-associated SNPs rs2156323 (VAV2) and rs2801219 (VAV3) and their flanking regions were screened by resequencing in a clinically well-characterized cohort of 537 subjects that included cases of POAG (n = 141), PACG (n = 111), and ethnically matched normal controls (n = 285). The data were analyzed by using appropriate statistical software. RESULTS: Resequencing of NTF4 revealed a nonsynonymous (A88V), silent (P151P) and two changes in the 3'UTR region, along with a known polymorphism (rs11669977) in cases of POAG; the PACG cases exhibited only the A88V variation. Of interest, the A88V mutation observed in Europeans was more prevalent in our normal control subjects (4.91%, 95% CI, 2.95-8.07) than in the POAG (2.14%, 95% CI, 0.73-6.11; P = 0.200) and PACG (2.85%, 95% CI, 0.97-8.06; P = 0.577) cases. There were no major differences in the presenting intraocular pressure, cup-to-disc ratio, and visual field defects among patients harboring the A88V variation. The other variations in NTF4 were not associated with the cases. The risk alleles of rs2156323 and rs2801219 in the Japanese were not associated with POAG (P = 0.533 and 0.133, respectively) and PACG (P = 0.223 and 0.394, respectively) in the Indian cohort. CONCLUSIONS: The present data indicate a lack of involvement of variations in NTF4, VAV2, and VAV3 with glaucoma pathogenesis in an Indian population.