Stuti Misra

Peripheral Neuropathy and Tear Film Dysfunction in Type 1 Diabetes Mellitus

Purpose. To compare tear film metrics in patients with type 1 diabetes mellitus (DM) and healthy controls and investigate the association between peripheral neuropathy and ocular surface quality. Methods. Dry eye symptoms were quantified in 53 patients with type 1 DM and 40 age-matched controls. Ocular examination included tear film lipid layer thickness grading, tear film stability and quantity measurement, and retinal photography. DM individuals additionally underwent a detailed neuropathy assessment. Results. Neither mean age nor dry eye symptom scores differed significantly between the DM and control groups (P = 0.12 and P = 0.33, resp.). Tear lipid thickness (P = 0.02), stability (P < 0.0001), and quantity (P = 0.01) were significantly lower in the DM group. Corneal sensitivity was also reduced in the DM group (P < 0.001) and tear film stability was inversely associated with total neuropathy score (r = −0.29, P = 0.03). Conclusion. The DM group exhibited significantly reduced tear film stability, secretion, and lipid layer quality relative to the age-matched control group. The negative correlation between tear film parameters and total neuropathy score suggests that ocular surface abnormalities occur in parallel with diabetic peripheral neuropathy.

Interocular Comparison by In Vivo Confocal Microscopy of the 2-Dimensional Architecture of the Normal Human Corneal Subbasal Nerve Plexus

Purpose: To investigate the configuration of the living human corneal subbasal nerve plexus in paired eyes of normal subjects using in vivo confocal microscopy. Methods: Laser scanning in vivo confocal microscopy was performed on both corneas of healthy human subjects, and a grid fixation pattern facilitated examination of consistent areas of central to midperipheral cornea. Macromedia/Adobe Freehand 10 was used to manually arrange images into contiguous montages. The subbasal nerve density and overall patterns were analyzed. Results: Both eyes of 6 subjects (3 women and 3 men, aged between 25 and 36 years) were examined. In all subjects, the subbasal nerve plexus exhibited a clockwise whorl configuration inferior to the central cornea. The mean subbasal nerve density at the whorl was 39.17 ± 4.95 mm/mm2 and 41.36 ± 4.19 mm/mm2 in the right and left eyes, respectively. There was no significant difference in the nerve density between the eyes (P = 0.61). Bland and Altman analysis confirmed high intraobserver repeatability and moderate interobserver repeatability. Conclusions: This study reveals the marked similarities between the corneal subbasal nerve plexus configuration in the right and left eyes of the living human cornea, highlighting that the typical mirror-image symmetry in corneal topographic patterns is not obeyed in respect to corneal innervation and that a clockwise orientation of the subbasal plexus is typically encountered. There was no statistical difference in the subbasal nerve density between the eyes.

Corneal microstructural changes in nerve fiber, endothelial and epithelial density after cataract surgery in patients with diabetes mellitus.

Purpose: The aim of this study was to analyze microstructural corneal changes following phacoemulsification of cataract with intraocular lens insertion in diabetes mellitus (DM). Methods: Prospective study of consecutive patients undergoing phacoemulsification with intraocular lens insertion, over a period of 6 months. Age, gender, serum glycosylated hemoglobin A1c levels, and effective phacoemulsification time were recorded. Anterior segment optical coherence tomography and corneal in vivo confocal microscopy were performed preoperatively and 1-month postoperatively. Subbasal nerve plexus (SBN) density, basal epithelial cell density, and endothelial cell density (ECD) were quantitatively analyzed. Results: Twenty-eight patients with type 2 DM (71.2 ± 7.6 years) and 23 healthy controls (mean age, 74.4 ± 7.4 years) were recruited. Mean hemoglobin A1c level was 7.5% in patients with DM and 5.7% in the control group (P < 0.0001). A significant reduction in SBN density was noted postoperatively in both DM (P < 0.0001) and non-DM groups (P < 0.0001). Patients with DM had a lower mean SBN density compared with non-DM group, before (P < 0.0001) and after surgery (P < 0.0001). Longer effective phacoemulsification time correlated with a greater decrease in ECD postoperatively in the whole cohort (P < 0.0001), and in the control (P = 0.002) and DM (P = 0.039) groups independently. There was no significant difference in the percentage decrease in ECD postoperatively between these 2 groups (P = 0.173). Conclusions: Subbasal nerve density is reduced after cataract surgery in patients with and without DM. However, lower initial SBN density in patients with DM may predispose them to develop diabetic keratopathy. DM does not predispose to greater endothelial loss following phacoemulsification.

Effect of Panretinal Photocoagulation on Corneal Sensation and the Corneal Subbasal Nerve Plexus in Diabetes Mellitus

PURPOSE To assess the effects of panretinal photocoagulation (PRP) for diabetic retinopathy (DR) on the human corneal subbasal nerve plexus (SBNP) and to investigate correlations between corneal subbasal nerve (SBN) density, corneal sensitivity, and diabetic peripheral neuropathy. METHODS Thirty-eight subjects with at least a 10-year history of diabetes mellitus (DM) or DR were included. Subjects were assigned to a PRP group (n = 19), having undergone a treatment of retinopathy in at least one eye or a non-PRP group (n = 19), with no history of PRP. The Michigan Neuropathy Screening Instrument (MNSI) was administered to enable quantification of neuropathic symptoms. Laser scanning in vivo confocal microscopy was performed to capture images of the corneal SBNP to allow determination of SBNP density. Central corneal sensitivity (CST) was evaluated by noncontact aesthesiometry and peripheral vibration perception threshold was measured with a biothesiometer. RESULTS Mean SBNP densities were 12.27 ± 4.28 mm/mm²) in the PRP group and 12.75 ± 3.59 mm/mm² in the non-PRP group. There were no significant differences in SBNP density (P = 0.71), CST (P = 0.84), MNSI score (P = 0.19), and biothesiometry (P = 0.77) between the PRP and non-PRP groups. When data from both groups (n = 38) were combined, corneal sensitivity was modestly correlated with SBNP density (r = 0.30, P = 0.06), and peripheral biothesiometry (r = 0.26, P = 0.11). CONCLUSIONS In DM correlation of corneal sensitivity, SBNP density, and peripheral biothesiometry may have a potential role in estimating the severity of peripheral neuropathy. Corneal SBNP density and sensitivity appear to be unaffected by PRP laser treatment compared with non-PRP diabetic eyes.

Impact of diabetes mellitus on the ocular surface: a review

Although diabetes mellitus is reaching epidemic proportions worldwide, ocular surface complications are still largely believed to be uncommon. Although these complications are not often sight threatening, the general well‐being of patients and the cost of their health care can be respectively compromised and added by them. Over the last decade, an association of ocular surface complications (in particular reduced corneal sub‐basal nerve density and corneal sensitivity) with peripheral neuropathy has emerged, which could help recognize the development of peripheral complications at an earlier stage and also provide research opportunities for examining new treatment modalities of diabetic neuropathies. The ocular surface complications of diabetes mellitus and their association with peripheral neuropathy are reviewed by this report.Although diabetes mellitus is reaching epidemic proportions worldwide, ocular surface complications are still largely believed to be uncommon. Although these complications are not often sight threatening, the general well-being of patients and the cost of their health care can be respectively compromised and added by them. Over the last decade, an association of ocular surface complications (in particular reduced corneal sub-basal nerve density and corneal sensitivity) with peripheral neuropathy has emerged, which could help recognize the development of peripheral complications at an earlier stage and also provide research opportunities for examining new treatment modalities of diabetic neuropathies. The ocular surface complications of diabetes mellitus and their association with peripheral neuropathy are reviewed by this report.

Vinpocetine regulates cation channel permeability of inner retinal neurons in the ischaemic retina.

Vinpocetine is a natural drug which exerts neuroprotective effects in ischaemia of the brain through actions on cation channels, glutamate receptors and other pathways. This study investigated the effect of vinpocetine on cation channel permeability of inner retinal neurons after acute retinal metabolic insult. We focused on amacrine and ganglion cells immunoreactive for calretinin or parvalbumin due to their previously documented susceptibility to ischaemia. Using the probe, 1-amino-4-guanidobutane (AGB), we observed increased cation channel permeability across amacrine and ganglion cells under ischaemia and hypoglycaemia but not anoxia. Calretinin and parvalbumin immunoreactivity was also reduced during ischaemia and hypoglyacemia but not anoxia. Vinpocetine decreased AGB entry into ischaemic and hypoglycaemic ganglion cells indicating that the drug can modulate unregulated cation entry. In addition, vinpocetine prevented the loss of calretinin and parvalbumin immunoreactivity following ischaemia suggesting it may indirectly regulate intracellular calcium. Vinpocetine also reduced AGB permeability in selected amacrine and ganglion cell populations following N-methyl-D-aspartate (NMDA) but not kainate activation suggesting that vinpocetines regulation of cation channel permeability may partly involve NMDA sensitive glutamate receptors.

In Vivo Confocal Microscopy of the Human Cornea in the Assessment of Peripheral Neuropathy and Systemic Diseases

In vivo confocal microscopy (IVCM) of the living human cornea offers the ability to perform repeated imaging without tissue damage. Studies using corneal IVCM have led to significant contributions to scientific and clinical knowledge of the living cornea in health and pathological states. Recently the application of corneal IVCM beyond ophthalmology to wider clinical and research fields has been demonstrated. Abnormalities of the corneal subbasal nerve plexus have been associated with many forms of peripheral neuropathy and Langerhans cells correlate with systemic inflammatory states. There is a rapidly growing evidence base investigating the use of corneal IVCM in many systemic conditions and a well-established evidence base for IVCM imaging of the corneal subbasal plexus in diabetic peripheral neuropathy. This paper reviews the potential use of corneal IVCM in general clinical practice as a noninvasive method of assessing peripheral neuropathies, monitoring inflammatory states and clinical therapeutic response.

Demographics and ocular biometric characteristics of patients undergoing cataract surgery in Auckland, New Zealand.

The aim is to investigate ethnic variation, in presentation and biometric parameters, within the population undergoing cataract surgery in Auckland.

Combining primary and piggyback intraocular lenses to treat extreme myopic astigmatism in stable keratoconus following cataract surgery

The majority of those with keratoconus can maximise visual acuity with spectacle or contact lens correction as they age; however, as subjects enter their sixties, cataracts may supervene and contact lens tolerance diminishes with consequent reduction in visual acuity. Following cataract extraction, the complex refractive error associated with keratoconus may not be readily corrected by an intraocular lens alone. This report highlights the planned implantation of a primary posterior chamber toric intraocular lens with a secondary piggyback, sulcus-based, intraocular lens in advanced but stable keratoconus with extreme myopic astigmatism and cataract.The majority of those with keratoconus can maximise visual acuity with spectacle or contact lens correction as they age; however, as subjects enter their sixties, cataracts may supervene and contact lens tolerance diminishes with consequent reduction in visual acuity. Following cataract extraction, the complex refractive error associated with keratoconus may not be readily corrected by an intraocular lens alone. This report highlights the planned implantation of a primary posterior chamber toric intraocular lens with a secondary piggyback, sulcus‐based, intraocular lens in advanced but stable keratoconus with extreme myopic astigmatism and cataract.

Compatibility of phospholipid liposomal spray with silicone hydrogel contact lens wear

PURPOSE To assess the effects of two weeks of regular phospholipid liposomal spray application on lipid layer grade, tear film stability, subjective comfort, visual acuity, and lipid deposition in silicone hydrogel contact lens wearers. METHODS Thirty-one existing contact lens wearers were enrolled and fitted with two week planned replacement silicone hydrogel contact lenses (Acuvue® Oasys®) in a prospective, randomized, paired-eye, investigator-masked trial. A phospholipid liposomal spray (Tears Again®) was applied to one eye (randomized) four times daily for two weeks. LogMAR high contrast visual acuity (VA), low contrast glare acuity (LCGA), non-invasive tear film break-up time (NIBUT), and lipid layer grade (LLG) were measured at baseline and day 14, in both treated and control eyes. Subjective comfort relative to baseline, and spectrofluorophotometric assessment of contact lens surface lipid deposition were also assessed on day 14. RESULTS All measurements did not differ at baseline between treated and control eyes. Lipid layer thickness and tear film stability were increased on day 14 in treated eyes (all p<0.05), but not in control eyes (all p>0.05). A greater proportion of participants reported improved comfort in the treated eye relative to the control eye (p=0.002). There were no significant differences in visual acuity or in contact lens surface lipid deposition, between treated and control eyes, on day 14 (all p>0.05). CONCLUSION The phospholipid liposomal spray increased tear film stability, lipid layer thickness and subjective comfort in silicone hydrogel contact lens wearers, without adversely affecting visual acuity or contact lens surface lipid deposition.