Changing face of glaucoma

Dear Friends,

Normal tension glaucoma (NTG), identified as early as 1857 by Von Graefe has clinical features similar to primary open angle glaucoma.[1] A prevalence of 0.2% was noted in 43-54-year-old age group and 1.6% in those over 75 years of age.[2] Risk factors that have been identified for NTG include elderly age, female gender, polymorphism of OPA1 gene, thin central corneal thickness, migraine and Raynaud's syndrome.[3] Diagnosis is attained at, if one or more of the following features are present: absent retinal pigment epithelium, cupping of fundus and splinter hemorrhages. The mainstay of management of NTG lies in the reduction of normal intraocular pressure, as discussed in collaborative NTG study.[4] Recently, many clinical studies have been conducted on NTG. Song et al., in this issue has published an in-depth analysis of the various anti-glaucomatic agents such as prostaglandin analogs, beta blockers and surgical corrections such as trabeculoplasty as treatment options for NTG from results obtained from previous studies. None of these have been shown to be good at neuroprotection while many other agents such as N-methyl-D-aspartate antagonist (memantine), a prostanoid (unoprostone), calcium channel blockers and statins are being evaluated for their neuroprotective effect in various clinical trials and Song et al., has also discussed these results in their review.

Congential glaucoma is a developmental disorder of childhood that is associated with elevated intraocular pressure, globe enlargement (buphthalmos), corneal edema, Haabstriae, optic nerve cupping, and atrophy.[5] It is a rare disorder with an incidence ranging between 1 in 1250 in Europeans to 1 in 12500 in Western population, attributed to goniodysgenesis caused by arrested development of chamber angle.[6] Both the eyes are affected in 4/5^th of the cases and prevalence is more in males.[7] Tamcelik et al., in this issue published an observational study wherein the demographic details of the patients with congenital glaucoma were evaluated in a developing country. Although majority of the observations were similar to other published studies,[6,8] the frequency of unilateral occurrence was found to be more in patients with secondary congenital glaucoma in the present study. This has been attributed to the presence of phakomatoses and Peters anomaly which presented unilaterally. Close to half of the study population have had consanguineous marriage and the study had not assessed various gene mutations such as CYP1B1, LTBP2 and MYOC, associated with the condition and this becoming the major limitation of the study.[9] Traditionally, goniotomy and trabeculotomy have been preferred but recently steon implantations, visualized cannulation, opening of Schlemm's canal, deep sclerectomy, trabectome and cytophotocoagulation have emerged as alternate options for managing congenital glaucoma.[10]

Cyclic fluctuations in intraocular pressure have been reported by various scientists since 1898.[11] This diurnal variation may confound the therapeutic effect of anti-glaucomatous medications.[12] Hence, monocular clinical trials have been conducted over years for various classes of anti-glaucomatic agents like beta-blockers, alpha agonists and prostaglandin analogs.[13,14,15] These studies not only have shed light on the efficacy of these medicines but also on the safety. Despite authors debate over the necessity of these uniocular trials, the preferred practice pattern guidelines of the American Academy of Ophthalmology recommends such trials to be conducted and is also widely agreed upon by many ophthalmologists.[16] Rao et al., in this issue has published a uniocular therapeutic trial with prostaglandin analogs. The authors have found an average reduction of intraocular pressure to around 40% in the contralateral untreated eye especially within first 12 hours with topical instillation of the drug. Earlier studies with a similar hypothesis[16,17] were contradictory to the present study. The current study being retrospective, and so the difference in the timing of measurement of intraocular pressure, “regression to mean” effect, inter observer variability cannot be ruled out and this becomes the limitation. Furthermore, the included data were obtained only from 30 patients. Nevertheless, the result of this study is a warning bell to those who keep the other eye as a control in measuring the effect of topical prostaglandin analogs.

Glaucoma being the second leading cause of blindness worldwide, several research studies are underway in the diagnosis and management of the same. Spectral domain optical coherence tomography has emerged as an objective way of measuring the retinal nerve fiber and the associated changes over time and is a boon to patients with glaucoma for early identification of neuropathy.[18] Similarly, ‘detection of apoptotic retinal cells’ has been developed that specifically looks at retinal ganglion cells and can be used to diagnose glaucoma even at very early stage.[19] A paradigm shift in research towards glaucoma treatment has been noted with the advent of stem cell and gene therapy. Various types of stem cells such as retinal stem cells, glial stem cells, retinal pigment epithelial stem cells, endothelial progenitor cells are being researched on to regenerate retinal neurons.[20] Similarly, in patients with inherited glaucoma, gene therapy and gene knockout strategies are also being explored as one of the possible options.[21]

As an additional bonus to the readers, Shome et al., in this issue has published a pre-clinical animal study on nanoparticulated carboplatin in the management of retinoblastoma. The most common type of cancer affecting the eye in children is retinoblastoma, which accounts for about 5-15% of all infant cancers.[22] The cancer cells are killed in a dose-dependent manner and therefore recently nanoparticle mediated chemotherapy administration has taken over great importance in the therapeutic field. In the present study, a high trans-scleral permeability with sustained levels of the drug in the vitreous humor was noted. Earlier studies in mice had found a significant reduction in tumor size with nanoparticle preparation of carboplatin.[23,24] Found to be promising in animal studies, a clinical trial has been conducted with the nanoparticle formulation of carboplatin and the results are corroborative with the present study.[25]

I am sure this issue will be an interesting read for all of us.

Happy reading!!!