Mindfulness Meditation Reduces Intraocular Pressure, Lowers Stress Biomarkers and Modulates Gene Expression in Glaucoma: A Randomized Controlled Trial.

BACKGROUND: Reducing intraocular pressure (IOP) in primary open-angle glaucoma (POAG) is currently the only approach to prevent further optic nerve head damage. However, other mechanisms such as ischemia, oxidative stress, glutamate excitotoxicity, neurotrophin loss, inflammation/glial activation, and vascular dysregulation are not addressed. Because stress is a key risk factor affecting these mechanisms, we evaluated whether mindfulness-based stress reduction can lower IOP and normalize typical stress biomarkers. MATERIALS AND METHODS: In a prospective, randomized trial 90 POAG patients (180 eyes; age above 45 y) were assigned to a waitlist control or mindfulness meditation group which practiced daily for 21 days. We measured IOP (primary endpoint), quality of life (QOL), stress-related serum biomarkers [cortisol, ß-endorphins, IL6, TNF-α, brain-derived neurotrophic factor (BDNF), reactive oxygen species (ROS), total antioxidant capacity (TAC)], and whole genome expression. RESULTS: Between-group comparisons revealed significantly lowered IOP in meditators (OD: 18.8 to 12.7, OS 19.0 to 13.1 mm Hg) which correlated with significantly lowered stress-biomarker levels including cortisol (497.3 to 392.3 ng/mL), IL6 (2.8 to 1.5 ng/mL), TNF-α (57.1 to 45.4 pg/mL), ROS (1625 to 987 RLU/min/104 neutrophils), and elevated ß-endorphins (38.4 to 52.7 pg/mL), BDNF (56.1 to 83.9 ng/mL), and TAC (5.9 to 9.3) (all P<0.001). These changes correlated well with gene expression profiling. Meditators improved in QOL (P<0.05). CONCLUSIONS: A short course of mindfulness-based stress reduction by meditation in POAG, reduces IOP, improves QOL, normalizes stress biomarkers, and positively modifies gene expression. Mindfulness meditation can be recommended as adjunctive therapy for POAG.

A Unique Case of JOAG With Lamellar Ichthyosis With Rickets: A Case Report and Review of the Literature.

PURPOSE: Ichthyosis is known to have ocular associations such as blepharitis, hypertrophic conjunctivitis, corneal vascularization, ectropion, lagophthalmos, etc. However, no reports of its association with glaucoma are there, to the best of our knowledge. We report a unique case of juvenile open-angle glaucoma (JOAG) with lamellar ichthyosis. METHOD: A 16-year-old male child presented with a gradual, painless progressive diminution of vision in both eyes over a period of 3 years. Systemic examination revealed stunted body growth with knock-knees, suggestive of late-onset rickets. Generalized dry scaly lesions with erythema, along with hyperkeratosis of the palms and the soles, suggestive of lamellar ichthyosis were present. On ocular examination, the intraocular pressure was 36 mm Hg; optic nerve head examination revealed a horizontally oval disc with near total cupping in the right eye and total cupping in the left eye, with extensive neuroretinal rim thinning and pallor. Gonioscopy showed wide open angles with prominent iris processes. Screening of JOAG-associated genes (MYOC, NTF4, WDR36, and CYP1B1) and ichthyosis-associated gene (TGM1) was performed by the direct PCR-sequencing method. RESULTS: A diagnosis of JOAG with advanced glaucomatous optic neuropathy with lamellar ichthyosis and rickets was made. The patient underwent right followed by left eye trabeculectomy with 0.2 mg/dL MMC (for 1 min). Postoperatively, the intraocular pressure was 8 mm Hg at 1 week, and 12 to 14 mm Hg at the 6-week, the 3-month, and the 6-month follow-up, and the visual acuity was maintained in the right eye. No mutations in MYOC, NTF4, WDR36, CYP1B1, and TGM1 were observed in the patient and his family. CONCLUSIONS: An association of glaucoma with ichthyosis should be kept in mind. Therefore, a detailed baseline ocular examination in children with ichthyosis is required, as early detection of glaucoma could prevent irreversible blindness.

Genetic, Biochemical and Clinical Insights into Primary Congenital Glaucoma.

Glaucoma is an irreversible form of optic neuropathy in which the optic nerve suffers damage in a characteristic manner with optic nerve cupping and retinal ganglion cell death. Primary congenital glaucoma (PCG) is an idiopathic irreversible childhood blinding disorder which manifests at birth or within the first year of life. PCG presents with a classical triad of symptoms (viz epiphora, photophobia and blepharospasm) though there are many additional symptoms, including large eye ball and hazy cornea. The only anatomical anomaly found in PCG is trabecular meshwork (TM) dysgenesis. PCG is an inheritable disease with established genetic etiology. It transmits through autosomal recessive mode. A number of cases are sporadic also. Mutations in many genes have been found to be causative in PCG and many are yet to be found. Mutations in cytochrome P4501B1 (CYP1B1) gene have been found to be the predominant cause of PCG. Other genes that have been implicated in PCG etiology are myocilin, Forkhead-related transcription factor C1 (FOXC1) and latent transforming growth factor beta-binding protein 2 (LTBP2). Mutations in these genes have been reported from many parts of the world. In addition to this, mitochondrial genome mutations are also thought to be involved in its pathogenesis. There appears to be some mechanism involving more than one genetic factor. In this review, we will discuss the various clinical, biochemical and genetic aspects of PCG. We emphasize that etiology of PCG does not lie in a single gene or genetic factor. Research needs to be oriented into a direction where gene-gene interactions, ocular embryology, ophthalmic metabolism and systemic oxidative status need to be studied in order to understand this disorder. We also accentuate the need for ophthalmic genetic facilities in all ophthalmology setups. How to cite this article: Faiq M, Sharma R, Dada R, Mohanty K, Saluja D, Dada T. Genetic, Biochemical and Clinical Insights into Primary Congenital Glaucoma. J Current Glau Prac 2013;7(2):66-84.