Holmes-Adie syndrome and vitamin B12 - associated peripheral neuropathy: An association or coincidence?

A 30-year-old male patient presented to the eye department with complaints of blurring of vision of right eye at distance and near for a duration of 1.5 months. Ocular examination revealed Anisocoria with enlarged pupil in the right eye. On instillation of 0.1% pilocarpine, there was a pronounced miosis in the dilated pupil seen at 30 min associated with an improvement in distance and near vision. On slit lamp examination, vermiform movements were seen in the affected pupil on shining the slit from temporal aspect. Fundus examination was within normal limits. Systemic examination revealed absent deep tendon reflexes. Based on the clinical features, a diagnosis of Holmes-Adie syndrome was reached and the patient was started on 0.1% pilocarpine eye drops. This case highlights the importance of thorough systemic examination and investigations in all cases of anisocoria.

A randomized pilot study to compare hair follicle cell suspensions prepared using trypsin alone versus trypsin in combination with collagenase type I for transplantation in vitiligo.

BACKGROUND: Noncultured extracted hair follicle outer root sheath cell suspension (NC-EHF-ORS-CS) is an upcoming surgical technique to treat stable vitiligo. Conventionally it employs trypsin to tap the hair follicle (HF) reservoir for autologous melanocytes and their precursors for transplantation. However, a perifollicular dermal sheath composed of type 1 collagen encases the target 'bulge' region of the HF. Adding collagenase type 1 would digest the ORS, facilitating better release of cells. AIM: To compare the repigmentation achieved using trypsin and a combination of collagenase plus trypsin, respectively, with dermabrasion alone, and to compare cell counts, viability and composition of both suspensions. METHODS: This was a randomized, double-blind, comparative, therapeutic trial, conducted as a pilot study on 22 patients with stable vitiligo. Three similar patches were randomized into three parallel treatment arms [(A) trypsin plus collagenase, (B) trypsin alone and (C) dermabrasion with vehicle alone]. Each patient's HF sample was divided and digested by the two methods, and transplanted as suspensions onto dermabraded patches, while a third dermabraded patch received the vehicle only. Suspensions were sent for laboratory analysis. Repigmentation was assessed over a follow-up of 6 months. RESULTS: There was a significant increase in cell yield and comparable viability when collagenase was added. Immunohistochemical and flow cytometry studies showed a nonsignificant increase in HMB45+ melanocytes and their precursor stem cells in group A. This trend was reflected clinically in the extent of repigmentation [group A (33.22%) > B (24.31%) > C (16.59%); P = 0.13]. Adding collagenase induced significantly higher repigmentation than dermabrasion alone (P < 0.05). CONCLUSIONS: Incorporating collagenase type I into the conventional NC-EHF-ORS-CS technique resulted in enhanced retrieval of pigment-forming cells and subsequently improved repigmentation in vitiligo.

Anterior segment changes on ultrasound biomicroscopy after intravitreal anti vascular endothelial growth factor injection.

BACKGROUND: Intravitreal injections are standard of care today and have the potential to change the anatomy of the anterior segment of the eye. This research was undertaken to evaluate the changes in anterior segment anatomy after intravitreal anti vascular endothelial growth factor (anti VEGF) injections. METHODS: We conducted a prospective interventional case series at a quaternary care center where patients undergoing intravitreal injection had pre and post injection ultrasound biomicroscopy (UBM) and intraocular pressure (IOP) measurement after intravitreal anti VEGF injection of 0.05 ml volume. RESULTS: 75 eyes of 75 patients as per inclusion criteria were studied. A transient rise in IOP post intravitreal injection was found immediately after the injection. The mean rise from baseline was 17 mmHg immediately after injection and IOP returned to normal within 30 min in all cases. Angle measurement done as per established techniques revealed no significant changes in the angles and anterior chamber. CONCLUSION: Intravitreal anti VEGF injections had no readily apparent short term concerns. IOP rise was transient and no case was found to have IOP high enough to cause concern for interruption of the optic nerve perfusion or statistically significant narrowing of the anterior chamber angle.

Alteration in regulatory T cells and programmed cell death 1-expressing regulatory T cells in active generalized vitiligo and their clinical correlation.

BACKGROUND: Vitiligo is an autoimmune depigmentation disease, and defects in regulatory T cells (Tregs) have been proposed in the pathogenesis of generalized vitiligo (GV). However, the role of programmed cell death (PD)1(+) Tregs has not been studied. OBJECTIVES: To investigate the status of Tregs, PD1(+) Tregs and associated parameters in active GV (aGV) during the first episode of disease attack and to establish the clinical correlation. METHODS: The percentages of circulating Tregs, PD1(+) Tregs and CD3(+) CD4(+) PD1(+) T cells were evaluated in 50 patients with aGV and 51 controls. Expression levels of FOXP3, TGFB1, CTLA4 and genes for chemokine receptors (CCR4, CCR7) and their ligands (CCL21, CCL22) were quantified in peripheral blood and in lesional, perilesional, nonlesional and normal skin sections. The corresponding proteins were immunolocalized in tissue of aGV. RESULTS: The percentage of Tregs was decreased (P = 0·001) and that of PD1(+) Tregs increased (P = 0·001) in peripheral blood of patients with aGV compared with controls. The abundance of TGFB1 and CCL21 mRNA was significantly decreased in the peripheral blood of patients with aGV. Significant differences in forkhead box P3, transforming growth factor-ß and CCL21 protein expression were found in skin sections. CONCLUSIONS: Deficiency in Treg frequency and decreased expression of Treg-associated parameters (TGFB and CCL21) suggested a possible defect in Tregs that may alter their suppression function and skin homing in aGV. The increased PD1(+) Tregs suggests that the PD1/PD ligand pathway may be involved in aGV and may have a role in Treg exhaustion. Further study is required to delineate the effect of PD1 in regulating Treg function in aGV.

Species-related pharmacological heterogeneity of histamine H(3) receptors.

We compared radioligand binding and functional data for histamine H(3) receptor ligands across different tissues or species to evaluate the basis for pharmacological evidence of receptor heterogeneity previously reported. Agonist binding affinities showed correlation coefficients near unity in comparing human, dog, rat, and guinea pig cerebral cortical histamine H(3) receptors. Antagonist binding affinities revealed lower correlations for human compared to dog, rat, or guinea pig, suggesting species-based pharmacological differences. The functional potencies of histamine H(3) receptor antagonists in field-stimulated guinea pig ileum were highly correlated to binding affinities for guinea pig, dog, and, to a lesser extent, rat cerebral cortex. However, antagonist binding affinity at human cerebral cortex did not correlate well with guinea pig ileum functional potency. These results suggest significant interspecies histamine H(3) receptor heterogeneity, consistent with recent receptor gene sequence data. Therefore, genetic heterogeneity, rather than peripheral and central histamine H(3) receptor diversity, is responsible for the pharmacological differences observed.

Voltage-activated potassium currents of rabbit osteoclasts: effects of extracellular calcium.

The effects of increased extracellular Ca2+ concentration ([Ca2+]e) were examined on a delayed-rectifier K+ current (IK) and an inward-rectifier K+ current (IK1) in rabbit osteoclasts. Elevation of [Ca2+]e from 1.8 to 18 mM shifted the half point for IK activation by +11.5 mV and the voltage dependence of inactivation by +9.7 mV and slowed the rate of IK activation and deactivation. These effects of elevated [Ca2+]e on IK are consistent with screening of cell surface negative charge. However, elevation of [Ca2+]e increased the voltage-dependent kinetics of IK inactivation at all potentials tested, inconsistent with that predicted by simple surface charge theory. This finding suggests an additional, regulatory role for [Ca2+]e in the gating of IK channels. Some osteoclasts had an IK1, which was decreased when [Ca2+]e was raised from 1.8 to 18 mM. The physiological function of both types of K+ currents remains to be determined, and it is not clear whether these currents are involved with the coupling of cytosolic [Ca2+] to [Ca2+]e.