Identification of tear-based protein and non-protein biomarkers: Its application in diagnosis of human diseases using biosensors.

Discovery of robust, selective and specific biomarkers are important for early diagnosis and monitor progression of human diseases. Eye being a common target for several human diseases, vision impediment and complications are often associated with systemic and ocular diseases. Tears are bodily fluids that are closest to eye and are rich in protein content and other metabolites. As a biomarker repository, it advantages over other bodily fluids due to the ability to collect it non-invasively. In this review, we highlight some recent advancements in identification of tear-based protein biomarkers like lacryglobin and cystatin SA for cancer; interleukin-6 and immunoglobulin-A antibody for COVID-19; tau, amyloid-ß-42 and lysozyme-C for Alzheimer's disease; peroxiredoxin-6 and α-synuclein for Parkinson's disease; kallikrein, angiotensin converting enzyme and lipocalin-1 for glaucoma; lactotransferrin and lipophilin-A for diabetic retinopathy and zinc-alpha-2 glycoprotein-1, prolactin and calcium binding protein-A4 for eye thyroid disease. We also discussed identification of tear based non-protein biomarkers like lysophospholipids and acetylcarnitine for glaucoma, 8-hydroxy-2'-deoxyquanosine and malondialdehyde for thyroid eye disease. We elucidate technological advancement in developing tear-based biosensors for diagnosis and monitoring diseases such as diabetes, diabetic retinopathy and Alzheimer's disease. Altogether, the study of tears as potential biomarkers for early diagnosis of human diseases is promising.

A rare case of Bardet-Biedl syndrome.

We report here a rare case of Bardet-Biedl syndrome (BBS). A 7-year-old boy was diagnosed to have BBS based on the clinical features: retinitis pigmentosa sine pigmento, obesity, postaxial polydactyly, syndactyly, and hypogenitalism. It was associated with mild hepatomegaly with deranged liver function test and mild renal involvement radiologically, high-arched palate, and low intelligence quotient. The patient was prescribed proper refractive correction and subjected to multidisciplinary management. BBS has ocular and systemic manifestations, requiring a multidisciplinary approach to treatment.

Association of Lipid Profile with Severity of Meibomian Gland Dysfunction.

INTRODUCTION: The impact of Meibomian gland dysfunction (MGD) on the overall health of the patient is not known. Efforts are being made to understand the association of dyslipidemia with MGD. The objective of the study was to determine the association of dyslipidemia with the severity of MGD, a contributor to dry eye syndrome. MATERIALS AND METHODS: We performed an observational case-control study at a tertiary care centre over 18 months and enrolled 116 patients in the age group of 18 to 65 years. A detailed history and clinical examination were done. Following examination, patients were allocated into two groups, patients with MGD and no history of dyslipidemia (cases) and patients without MGD and no history of dyslipidemia (controls). A fasting lipid profile was done for both these groups. The data were subsequently analyzed with SPSS software. RESULTS: Fifty six (48.3%) of the participants had serum total cholesterol levels ≥200 mg/dl, with a significant association between higher cholesterol levels and severity of MGD (p=0.0001). 77 (66.4%) of the participants had serum triglycerides levels of ≥150 mg/ dl. There was a significant association between the severity of MGD and elevated triglyceride levels (95% confidence interval of Pearson's chi-square 28.16, p=0.0001). A significant association was also observed between the severity of MGD and elevated LDL levels (95% confidence interval of Pearson's chi-square 5.95, p=0.015). However, no association was found between HDL levels and the severity of MGD. CONCLUSION: The results suggest that patients with MGD and without any history of dyslipidemia, may have higher blood levels of lipid profile components as compared to age-matched controls.

Waardenburg syndrome with dry eyes: A rare association.

Waardenburg syndrome (WS) is a rare congenital disorder primarily characterized by characteristic facial abnormalities as dystopia canthorum and synophrys; depigmentation of the hair, skin (premature graying of hair), and/or the iris of both eyes; and/or congenital deafness. Here, we report a rare case of WS with associated dry eyes. A 4-year-old female presented with blue eyes and no tear and nasal secretion production since birth. She was also deaf and dumb since birth. On examination, it was recognized as an atypical case of WS type 2 clinically, with several classical features such as white forelock, bilateral blue iris, hypopigmented fundus, smooth philtrum, bilateral profound hearing loss, and a rare association of bilateral dry eyes. The patient was given proper refractive correction, treatment of her dry eyes, and subjected to multidisciplinary approach as for the management of sensorineural hearing loss. It was a case of WS type 2 with a rare association of bilateral dry eyes.

Influence of Glycated Haemoglobin Levels on Intraocular Pressure in patients with Type -II Diabetes Mellitus.

INTRODUCTION: Patients with diabetes mellitus are at a higher risk of developing primary open angle glaucoma (POAG) as compared to non-diabetic patients. OBJECTIVES: To determine whether there is a correlation between hyperglycemic levels and intraocular pressure (IOP) and to identify patients of Type II diabetes mellitus who are at a higher risk of developing glaucoma. MATERIALS AND METHODS: This was a hospital based, cross sectional study performed on patients with type II diabetes mellitus, at a tertiary health care center in Uttarakhand, India between July, 2018 and September, 2018. 318 eyes of 159 patients with Type2 diabetes mellitus were included in the study. IOP was measured by Goldmannappla nation to no meter and central corneal thickness was measured with specula microscope in all patients, in addition to glycated hemoglobin levels (HbA1c) and fasting and post-prandial blood glucose levels. The data was analysed using SPSS 22 software. RESULTS: Mean IOP was found to be 15.75 ± 3.18 mm Hg in patients with HbA1c levels between 6.5%-12% (Group I) and 17.42 ± 2.67 mm Hg in patients with HbA1c levels more than 12 % (Group II). The difference between the two groups was statistically significant (P =0.013). Out of 159 patients with Type 2 Diabetes mellitus, a total of 11 patients had IOP more than 21mm Hg in one or both the eyes. CONCLUSION: Hyperglycaemic levels as determined by raised HbA1c levels are associated with higher intraocular pressures in patients with type 2 diabetes mellitus.

Anterior transposition of inferior oblique for inferior rectus muscle aplasia.

Congenital absence of extraocular muscle is rare. The most common extraocular muscle found to be congenitally absent is superior oblique followed by inferior rectus. Patients with absent inferior rectus muscle can present with abnormal head posture and incomitant hypertropia with limitation of ocular motility in the field of action of the inferior rectus with or without torticollis. Microphthalmos, microcornea, coloboma, and Axenfeld-Rieger syndrome are known to be commonly associated with inferior rectus muscle aplasia. Orbital computed tomography (CT) or magnetic resonance imaging before surgery is useful for confirmation of the diagnosis and plan of management. We report satisfactory surgical outcome of anterior transposition of inferior oblique in a case of inferior rectus aplasia with iris coloboma, microcornea, and anomalous insertion of inferior oblique. The patient had right hypertropia in primary position which increased on levoversion and left tilt. Preoperative orbital CT revealed congenital absence of inferior oblique. Peroperatively, congenital absence of inferior rectus was confirmed, and inferior oblique was found to be hyperplastic and abnormally inserted to the sclera. Anterior transposition of inferior oblique was done with satisfactory outcome.

Pharmacological therapy for amblyopia.

Amblyopia is the most common cause of preventable blindness in children and young adults. Most of the amblyopic visual loss is reversible if detected and treated at appropriate time. It affects 1.0 to 5.0% of the general population. Various treatment modalities have been tried like refractive correction, patching (both full time and part time), penalization and pharmacological therapy. Refractive correction alone improves visual acuity in one third of patients with anisometropic amblyopia. Various drugs have also been tried of which carbidopa & levodopa have been popular. Most of these agents are still in experimental stage, though levodopa-carbidopa combination therapy has been widely studied in human amblyopes with good outcomes. Levodopa therapy may be considered in cases with residual amblyopia, although occlusion therapy remains the initial treatment choice. Regression of effect after stoppage of therapy remains a concern. Further studies are therefore needed to evaluate the full efficacy and side effect profile of these agents.

Glaucoma in Asia- An epidemiological perspective.

Glaucoma is the third most common cause of global visual impairment. Bilateral blindness from glaucoma is projected to affect greater than 11 million individuals worldwide by the year 2020, with a disproportionately large number of the affected individuals being of Asian descent. The disease pattern, its response to treatment, and ground realities differ among various Asian countries. Over the past decade, there have been tremendous efforts for combating cataract blindness, but unfortunately few efforts in Asian countries have been made to establish comprehensive eye care programs in the community that include management of glaucoma. There is a need for education about the disease amongst the general public and continuing medical education and training of practicing ophthalmologists in addition to improvement of infrastructure to combat blindness due to glaucoma.

Congenital cranial dysinnervation disorders.

The European Neuromuscular Centre (ENMC) derived the term Congenital Cranial Dysinnervation Disorders in 2002 at an international workshop for a group of congenital neuromuscular diseases. CCDDs are congenital, non-progressive ophthalmoplegia with restriction of globe movement in one or more fields of gaze. This group of sporadic and familial strabismus syndromes was initially referred to as the 'congenital fibrosis syndromes' because it was assumed that the primary pathologic process starts in the muscles of eye motility. Over the last few decades, evidence has accumulated to support that the primary pathologic process of these disorders is neuropathic rather than myopathic. This is believed that for normal development of extra ocular muscles and for preservation of muscle fiber anatomy, normal intra-uterine development of the innervation to these muscles is essential. Congenital dysinnervation to these EOMs can lead to abnormal muscle structure depending upon the stage and the extent of such innervational defects. Over last few years new genes responsible for CCDD have been identified, permitting a better understanding of associated phenotypes, which can further lead to better classification of these disorders. Introduction of high-resolution MRI has led to detailed study of cranial nerves courses and muscles supplied by them. Thus, due to better understanding of pathophysiology and genetics of CCDDs, various treatment modalities can be developed to ensure good ocular alignment and better quality of life for patients suffering from the same.

Impact of Superior Oblique Transposition on Primary Position Deviation, a Pattern and Intorsion in Third Nerve Palsy.

PURPOSE: To evaluate the role of superior oblique transposition on primary position alignment, A pattern, and intorsion in third nerve palsy. METHODS: Ten patients with isolated, unilateral third nerve palsy were included in this prospective study. The patients were treated by conventional surgery on horizontal recti together with superior oblique transposition by Scott's procedure in the paretic eye. RESULTS: Pre-operative primary horizontal deviation was 60-80 PD (mean 70.00±7.45 PD). Pre-operative primary hypotropia was 15-22 PD (mean 18.80±2.48 PD). Mean A-pattern was 17.80±2.65 PD. All patients included in the study had some degree of objective torsion as measured by Guyton's method. One patient had grade I objective intorsion, 2 had grade II, 6 had grade III, and 1 had grade IV objective intorsion. Primary position horizontal alignment (up to ±8 PD) was achieved in 9 patients. Primary position vertical alignment (up to ±8 PD) was achieved in all 10 patients. Only 2 of 10 patients had A-pattern of 10 PD, in the remaining 8 patients it was eliminated (P<0.05). Postoperatively, 5 patients had no objective intorsion and 5 had grade I intorsion, and none of the patients had hypertropia or paradoxical eye movements. CONCLUSION: Superior oblique transposition by Scott's procedure along with conventional surgery on horizontal recti in third nerve palsy results in better horizontal and vertical alignment, and improves A-pattern and intorsion, thus leading to better binocular interaction.

An update on Anti-inflammatory Compounds: A Review.

Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process. Also, it has been reported to be associated with the onset of various cancers. An effective anti-inflammatory drug should be able to inhibit the development of inflammation without interfering in normal homeostasis. Current approaches to overcome the inflammation include the use of immune selective anti-inflammatory derivatives, selective glucocorticoid receptor agonist, resolvins and protectins and TNF inhibitors. A number of herbal drugs have been identified in the past that can target inflammatory cytokines. This review mainly focuses on the newer molecules to combat the inflammation and also emphasise on various studies carried out in the past. Thus, the high prevalence of inflammation obliges the development of new drugs; therefore, a safe and efficient drug molecule to confer protection against inflammation is urgently needed.