Pituitary Dysfunction in Idiopathic Intracranial Hypertension: An Analysis of 80 Patients.

BACKGROUND: Empty sella is a commonly described imaging entity in patients with idiopathic intracranial hypertension (IIH). Though menstrual and hormonal disturbances have been associated with IIH, available literature lacks systematic analysis of pituitary hormonal disturbances in IIH. More so, the contribution of empty sella in causing pituitary hormonal abnormalities in patients of IIH has not been described. We carried out this study to systematically assess the pituitary hormonal abnormalities in patients with IIH and its relation to empty sella. METHODS: Eighty treatment naïve patients of IIH were recruited as per a predefined criterion. Magnetic resonance imaging (MRI) brain with detailed sella imaging and pituitary hormonal profile were done in all patients. RESULTS: Partial empty sella was seen in 55 patients (68.8%). Hormonal abnormalities were detected in 30 patients (37.5%), reduced cortisol levels in 20%, raised prolactin levels in 13.8%, low thyroid-stimulating hormone (TSH) levels in 3.8%, hypogonadism in 1.25%, and elevated levels of gonadotropins were found in 6.25% of participants. Hormonal disturbances were independent and were not associated with the presence of empty sella (p = 0.493). CONCLUSION: Hormonal abnormalities were observed in 37.5% patients with IIH. These abnormalities did not correlate with the presence or absence of empty sella. Pituitary dysfunction appears to be subclinical in IIH and responds to intracranial pressure reduction, not requiring specific hormonal therapies.

Correlation of angiogenic growth factors and inflammatory cytokines with the clinical phenotype of ocular tuberculosis.

PURPOSE: To determine the correlation of angiogenic growth factors and inflammatory cytokines with the clinical phenotype of ocular tuberculosis (OTB). METHODS: Vitreous fluid was analysed for cytokines in patients with OTB and non-OTB uveitis using multiplex fluorescent bead-based flow cytometric assay. The clinical phenotypes were recorded and correlated with vitreous biomarkers. RESULTS: Vitreous humour from OTB patients had elevated levels of interleukin-10 (IL-10), IL-17-A, interferon-gamma (IFN-γ), and tumour necrosis factor-alpha (TNF-α). Angiopoietin (Ang-2) levels were higher in the panuveitis phenotype. OTB posterior uveitis phenotype had relatively higher vascular endothelial growth factor (VEGF) levels and lower fibroblast growth factor (FGF) levels. Additionally, eyes with choroiditis and vasculitis had elevated levels of VEGF and Ang-2 with FGF downregulation. Both IFN-γ and IL-10 were upregulated in the choroiditis phenotype of OTB. CONCLUSION: Angiogenic growth factors and inflammatory cytokines were altered in the vitreous humour of OTB patients. IFN-γ, VEGF, and IL-10 levels are increased in choroiditis and vasculitis phenotypes. Receiver operating characteristic (ROC) curve analysis further emphasized the importance of the IFN-γ assay in the diagnosis of OTB.

Displacement of Submacular Hemorrhage With Vitrectomy Combined With Subretinal Balanced Salt Solution and Air.

PURPOSE: To describe a technique of displacement of submacular hemorrhage (SMH) using subretinal injection of balanced salt solution and filtered air. METHODS: Patients presenting within 2 weeks of massive SMH (>4 disk diameter) were prospectively included. All patients underwent 25-gauge pars plana vitrectomy, posterior vitreous detachment, injection of subretinal balanced salt solution and filtered air followed by partial fluid air exchange, 20% sulfur hexafluoride tamponade, and heads-up positioning postoperatively. Degree of displacement of SMH was assessed at 1 month and change in best-corrected visual acuity was assessed at 3 months. RESULTS: Ten patients with massive SMH who underwent the aforementioned procedure were included. Complete displacement of bleed from the macula was achieved in nine (90%) of 10 eyes at 1 month. There was significant improvement in best-corrected visual acuity from baseline at 1 month ( P = 0.015) and 3 months ( P = 0.043). CONCLUSION: Pars plana vitrectomy with injection of subretinal balanced salt solution and filtered air was well-tolerated and efficacious in displacing large and thick SMH in patients operated within 2 weeks of onset of symptoms.

Serum Calcitonin Gene-Related Peptide Is Elevated in Patients With Migraine and Ophthalmoplegia.

BACKGROUND: There is ongoing debate about whether the oculomotor (III), trochlear (IV), or abducens (VI) nerve paresis in patients with migraine is directly attributable to migraine (ophthalmoplegic migraine [OM]) or is due to an inflammatory neuropathy (recurrent painful ophthalmoplegic neuropathy [RPON]). As migraine is associated with elevated serum calcitonin gene-related peptide (CGRP) levels, we studied serum CGRP levels among patients with OM/RPON to determine whether they are elevated during and between attacks. This is the first study assessing CGRP levels in the serum of patients with OM/RPON. METHODS: The aim of this case-control study was to assess serum CGRP levels in patients with ophthalmoplegia and a headache consistent with migraine according to ICHD-3 criteria. Serum CGRP levels were measured during the ictal and interictal phases in 15 patients with OM/RPON and compared with age-matched and sex-matched controls without migraine (12 patients). RESULTS: The median serum CGRP levels were significantly elevated ( P = 0.021) during the ictal phase (37.2 [36.4, 43.6] ng/L) compared with controls (32.5 [30.1, 37.3] ng/L). Serum CGRP levels during the attack correlated with the total duration of ophthalmoplegia. A CGRP level of 35.5 ng/L in the ictal phase of the attack had a sensitivity of 86.7% and specificity of 75.0% in diagnosing a patient with OM/RPON. CONCLUSIONS: Elevated serum CGRP levels during the ictal phase of OM/RPON favor migraine as the underlying cause of episodic headache with ophthalmoplegia.

Systemic biomarkers of retinopathy of prematurity in preterm babies.

PURPOSE: Retinopathy of prematurity (ROP) progression is an inter-play of various perinatal and neonatal angiogenic and inflammatory cytokines. A small subset of ROP progresses to ROP requiring treatment. The present study was conducted with the aim to determine whether levels of IL-6, IL-8 and VEGF in serum and urine at the time of first ROP screening visit could be a biomarker for the prediction of development of treatable ROP. METHOD: Prospective single-center observational study of preterm babies screened for ROP. Blood and urine samples were collected as a part of routine sampling at initial ROP screening visit and stored at -80 °C for further processing. The babies were followed up and grouped into 'Group A' comprising of 35 babies who developed treatable ROP and 'Group B' comprising of 36 babies with regressed ROP or no ROP. The evaluation of blood and urine samples was done for IL6, IL8 and VEGF by solid-phase sandwich RayBio® Human ELISA kit. RESULTS: The median serum values for IL-6, IL-8 and VEGF in Group A and Group B were 5.8 pg/ml (IQR 1.5,128.5) and 8.7 pg/ml (IQR 1.5,30.5), 55.9 pg/ml (IQR 28.0, 392.9) and 27.0 pg/ml (IQR 20.5,444.9) and 26.6 pg/ml (IQR 6.3, 39.4) and 30.0 pg/ml (IQR9.2,70.3), respectively. Group A had significantly increased levels of IL-8 (p < 0.05). However, AUROC curve for serum IL-8 demonstrated suboptimal discriminating ability. CONCLUSION: Babies developing ROP requiring treatment had significantly increased levels of IL-8 in the serum at the time of initial screening. However, it could not serve as predictor for treatable ROP.

MULTICOLOR CONFOCAL SCANNING LASER OPHTHALMOSCOPE IMAGING IN POSTERIOR UVEITIS.

PURPOSE: To study the utility of MultiColor confocal scanning laser ophthalmoscope imaging (MCI) in identifying the morphology of uveitic lesions compared with conventional color fundus photography (CFP) in patients with posterior uveitis. METHODS: In this prospective observational study, subjects with posterior uveitis underwent MCI and CFP. The images obtained by the two modalities were analyzed by two independent reviewers for vitreoretinal surface abnormalities, retinal fluid and hemorrhages, and depth/location of lesions. These findings were compared with the clinical findings and other imaging techniques. RESULTS: Sixty-nine eyes of 43 patients (25 men) with mean age of 33.5 ± 13.9 years were studied. MultiColor imaging had better sensitivity and specificity in detecting vitreoretinal interface abnormalities, such as epiretinal membrane and inner retinal striae, compared with CFP. MultiColor imaging failed to detect retinochoroiditis lesions in 5 of 6 eyes (83%) and choroiditis in 9 46 eyes (20%), which were detected on CFP and clinical examination. Also, MCI showed a high false-positive rate of 34% in detecting intraretinal hemorrhages. CONCLUSION: Retinochoroidal lesions in posterior uveitis may be poorly identified on MCI compared with CFP and clinical examination. One must exercise caution in commenting on disease morphology based on MCI alone.

Enzymatic vitreolysis using reengineered Vibrio mimicus-derived collagenase.

Purpose: Collagen is a key player contributing to vitreoelasticity and vitreoretinal adhesions. Molecular reorganization causes spontaneous weakening of these adhesions with age, resulting in the separation of the posterior hyaloid membrane (PHM) from the retina in what is called complete posterior vitreous detachment (PVD). Incomplete separation of the posterior hyaloid or tight adherence or both can lead to retinal detachment, vitreomacular traction syndrome, or epiretinal membrane formation, which requires surgical intervention. Pharmacological vitrectomy has the potential of avoiding surgical vitrectomy; it is also useful as an adjunct during retinal surgery to induce PVD. Previously studied enzymatic reagents, such as collagenase derived from Clostridium histolyticum, are nonspecific and potentially toxic. We studied a novel collagenase from Vibrio mimicus (VMC) which remains active (VMA), even after deletion of 51 C-terminal amino acids. To limit the activity of VMA to the vitreous cavity, a fusion construct (inhibitor of hyaluronic acid-VMA [iHA-VMA]) was made in which a 12-mer peptide (iHA, which binds to HA) was fused to the N-terminus of VMA. The construct was evaluated in the context of PVD. Methods: VMA and iHA-VMA were expressed in Escherichia coli, purified, and characterized with gelatin zymography, collagen degradation assay, fluorescamine-based assay, and cell-based assays. Two sets of experiments were performed in New Zealand albino rabbits. Group A (n = 10) received iHA-VMA, while group B (n = 5) received the equivalent dose of VMA. In both groups, saline was injected as a control in the contralateral eyes. Animals were monitored with indirect ophthalmoscopy, optical coherence tomography (OCT), and B-scan ultrasonography. Retinal toxicity was assessed with hematoxylin and eosin (H&E) staining of retinal tissue. Results: The activity of iHA-VMA and VMA was comparable and 65-fold lower than that of C. histolyticum collagenase Type IV. In the iHA-VMA group, all the rabbits (n = 10) developed PVD, with complete PVD seen in six animals. No statistically significant histomorphological changes were seen. In the VMA group, four of the five rabbits developed complete PVD; however, retinal morphological changes were seen in two animals. Conclusions: iHA-VMA displays targeted action confined to the vitreous and shows potential for safe pharmacologic vitreolysis.

BACILLARY LAYER DETACHMENT IN ACUTE VOGT-KOYANAGI-HARADA DISEASE: A Novel Swept-Source Optical Coherence Tomography Analysis.

PURPOSE: To report the frequency, optical coherence tomography (OCT) findings, and visual and anatomic outcomes of patients with acute Vogt-Koyanagi-Harada disease presenting with the bacillary layer detachment (BLD) (intraretinal split at the photoreceptor inner segment myoid). METHODS: This was a retrospective analysis of a consecutive series of patients with Vogt-Koyanagi-Harada disease having a minimum follow-up of 6 months. All patients had swept-source OCT, fluorescein angiography, and indocyanine green angiography performed at baseline. The characteristics of serial swept-source OCT were recorded and analyzed. RESULTS: Sixty-two subjects (42 women; age: 34.2 ± 12 years) with Vogt-Koyanagi-Harada disease were included. 118 eyes (95.2%) had serous retinal detachment at presentation. 112 eyes (94.9%) showed the BLD at baseline. In 8 of 112 (7.1%) eyes with the BLD, the external limiting membrane at the anterior aspect of the BLD showed focal discontinuity. The interdigitation zone at the base of the BLD showed discontinuity in 53 of 112 (47.3%) eyes with the BLD. The ellipsoid zone could not be identified as a separate hyperreflective line at the base of the BLD in 102 of 112 eyes (91.1%). Bacillary layer detachments resolved within 3.4 ± 1.3 days after intravenous methylprednisolone therapy with improvement in the best-corrected visual acuity from 0.96 to 0.4 logarithm of the minimum angle of resolution (20/184 Snellen's equivalent) (P < 0.001). Resolution of serous retinal detachment was observed after 5.9 ± 2.6 days. CONCLUSION: In eyes with acute Vogt-Koyanagi-Harada disease, the BLD is a common finding and represents a split in the photoreceptor layer at the inner segment myoid and can be differentiated from serous retinal detachment using swept-source OCT. In addition, resolution of the BLD and photoreceptor recovery can be evaluated using serial swept-source OCT.

High-altitude pulmonary oedema: Newer treatment modalities for an age-old problem.

Background & objectives: High-altitude pulmonary oedema (HAPE) continues to challenge the healthcare providers at remote, resource-constrained settings. High-altitude terrain itself precludes convenience of resources. This study was conducted to evaluate the rise in peripheral capillary saturation of oxygen (SpO2) by the use of a partial rebreathing mask (PRM) in comparison to Hudson's mask among patients with HAPE. Methods: This was a single-centre, randomized crossover study to determine the efficiency of PRM in comparison to Hudson's mask. A total of 88 patients with HAPE referred to a secondary healthcare facility at an altitude of 11,500 feet from January to October 2013 were studied. A crossover after adequate wash-out on both modalities was conducted for first two days of hospital admission. All patients with HAPE were managed with bed rest and stand-alone oxygen supplementation with no adjuvant pharmacotherapy. Results: The mean SpO2on ambient air on arrival was 66.92±10.8 per cent for all patients with HAPE. Higher SpO2values were achieved with PRM in comparison to Hudson's mask on day one (86.08±5.15 vs. 77.23±9.09%) and day two (89.94±2.96 vs. 83.39±5.93%). The difference was more pronounced on day one as compared to day two. Interpretation & conclusions: Mean SpO2values were found to be significantly higher among HAPE patients using PRM compared to those on Hudson's mask. Further studies to understand the translation of this incremental response in SpO2to clinical benefits (recovery times, mortality rates and hospital stay) need to be undertaken.

Sodium fluorescein dye as an adjunct in vitrectomy for rhegmatogenous retinal detachment in oculocutaneous albinism.

A 48-year-old male with oculocutaneous albinism (OCA) presented with bilateral diminution of vision. Ocular examination revealed bilateral central corneal thinning, scarring with ectasia, depigmented irides, transillumination defects, and pseudophakia. Examination of the right eye also revealed a hyperoleon, emulsified silicon oil in the vitreous cavity, and an attached retina, while the left eye had a total rhegmatogenous retinal detachment (RRD). This case describes a unique set of challenges (the presence of an ectatic scarred cornea and a hypopigmented fundus) and sodium fluorescein dye as an adjunct in the surgical management of a complex RRD. A review of literature highlighting the association of keratoconus and RRD in OCA is also presented in this report.

Diagnostic Accuracy of Pediatrician-performed Digital Retinal Imaging with 3nethra neo for ROP Screening.

OBJECTIVES: To evaluate the accuracy of pediatrician-performed wide-field digital retinal imaging (WFDRI) for diagnosing Retinopathy of prematurity (ROP), as compared to binocular indirect ophthalmoscopy (BIO) as the reference standard. METHODS: Eligible infants undergoing ROP screening were enrolled consecutively. BIO was performed by trained ophthalmologists, followed by WFDRI (using "3nethra neo" camera) by a pediatrician. An expert pediatric ophthalmologist reviewed de-identified images for quality, presence, and severity of ROP. She was masked to the findings of BIO and the pediatrician. Diagnostic accuracy for detecting any ROP, ROP requiring treatment (Type 1), and ROP requiring referral (Type 1 or 2) were calculated for WFDRI, considering BIO as the reference standard. RESULTS: The analysis included 427 eyes. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic accuracy, and diagnostic odds ratio of WFDRI were 0.88 (95% CI: 0.81, 0.93), 0.89 (0.85, 0.92), 7.8 (5.7, 10.9), 0.14 (0.09, 0.21), 0.89 (0.85, 0.91), and 58.3 (31, 110) respectively for detection of 'any ROP'. For detecting ROP requiring treatment (Type 1), the sensitivity, specificity, NLR, and diagnostic accuracy were 0.90 (0.75, 0.97), 1.00 (0.99, 1.00), 0.11 (0.04, 0.27), and 0.99 (0.98, 1.00) respectively. For ROP requiring referral, the sensitivity, specificity, NLR, and diagnostic accuracy of pediatrician-performed WFDRI were 0.92 (0.80, 0.98), 1.00 (0.99, 1.00), 0.08 (0.03, 0.21), and 0.99 (0.98, 1.00) respectively. No serious adverse events were noted. The pediatrician and ophthalmologist had a near-perfect (k-1.00) and strong (k-0.88) agreement for ROP requiring treatment and any ROP, respectively. CONCLUSIONS: Pediatrician-performed WFDRI is feasible, safe, and has excellent diagnostic accuracy for identifying ROP requiring treatment.

Use of the Aurolab Aqueous Drainage Implant as a buckling element in pediatric retinal detachment with a preexisting glaucoma drainage device.

Purpose: To describe a novel technique for repair of rhegmatogenous retinal detachment in an eye with a previous non-valved glaucoma drainage device, the Aurolab Aqueous Drainage Implant (AADI). Observations: A 5-year-old child with bilateral primary congenital glaucoma presented with an inferior retinal detachment (RD) in the left eye. The left eye had a history of multiple surgical interventions including combined trabeculotomy and trabeculectomy done twice, AADI implantation and subsequently phacoaspiration with IOL implantation, 18 months prior to presentation. The left eye retinal detachment was managed by scleral buckling technique using the plate of the AADI as a buckling element without its explantation. Conclusions: AND IMPORTANCE: Management of retinal detachment in eyes with a pre-existing glaucoma drainage device (GDD) is uniquely challenging. Explantation of the GDD would likely result in intractable glaucoma post-operatively, requiring another surgery. Use of the trimmed plate of the GDD itself as the buckling element helped in settling the RD and preserving intraocular pressure control.

Papillomacular bundle sparing versus conventional internal limiting membrane peeling for idiopathic macular hole ≤400 µm.

Purpose: To compare the outcomes of papillomacular bundle (PMB) sparing internal limiting membrane (ILM) peeling (group LP) and conventional ILM peeling (group CP) for treatment of idiopathic macular hole (MH) of ≤400 µm. Methods: Fifteen eyes were included in each group. In group CP, conventional 360° peeling was done, while in group LP, ILM was spared over PMB. The changes in peripapillary retinal nerve fiber layer (pRNFL) thickness and ganglion cell-inner plexiform layer (GC-IPL) thickness were analyzed at 3 months. Results: MH was closed in all with comparable visual improvement. Postoperatively, retinal nerve fiber layer (RNFL) was significantly thinner in the temporal quadrant in group CP. GC-IPL was significantly thinner in the temporal quadrants in group LP, whereas it was comparable in group CP. Conclusion: PMB sparing ILM peeling is comparable to conventional ILM peeling in terms of closure rate and visual gain, with the advantage of less retinal damage at 3 months.

Retinopathy of Prematurity and Glucose-6-Phosphate Dehydrogenase Activity: A Case-Control Study.

OBJECTIVE: To determine whether red blood cell glucose-6-phosphate dehydrogenase (G6PD) activity is associated with retinopathy of prematurity (ROP). METHODS: This case-control study was conducted in a Level-3 neonatal unit. Subjects were inborn boys with birth weight <2000 g. "Cases" were consecutive subjects with ROP of any severity. "Controls" were consecutive unrelated subjects without ROP. Recipients of blood or exchange transfusions were excluded. Sixty cases (out of 98 screened) and 60 controls (out of 93 screened) were enrolled. G6PD activity (quantitative assay) as the candidate risk factor was evaluated. RESULTS: Sixty cases with 60 controls [mean (SD) gestation 28.80 (2.2) and 30.60 (2.2) wk respectively] were compared. "Cases" had a higher median (1st, 3rd quartile) G6PD activity compared to "controls" [7.39 (4.7, 11.5) vs. 6.28 (4.2, 8.8) U/g Hb, p = 0.084]. G6PD activity was highest among ROP requiring treatment [8.68 (4.7, 12.3)] followed by ROP not requiring treatment [6.91 (4.4, 11.0)], followed by controls (plinear trend = 0.06). Gestation, birth weight, duration of oxygen, breastmilk feeding, and clinical sepsis were other variables associated with ROP on univariable analysis. On multivariable logistic regression, G6PD activity [Adjusted OR 1.14 (1.03, 1.25), p = 0.01] and gestation [Adjusted OR 0.74 (0.56, 0.97), p = 0.03] independently predicted ROP. C-statistic of the model was 0.76 (95% CI 0.67, 0.85). CONCLUSIONS: Higher G6PD activity was independently associated with ROP after adjusting for confounders. Each 1 U/g Hb increase in G6PD increased the odds of ROP by 14%. Severer forms of ROP were associated with higher levels of G6PD activity.

Endogenous Endophthalmitis in COVID-19 Patients: A Case Series and Literature Review.

PURPOSE: To report outcomes in cases of endogenous endophthalmitis (EE) following COVID-19 infection. MATERIAL AND METHODS: In a retrospective study, patients with EE, who had a recent history of COVID-19 infection requiring hospital admission were recruited. Necessary demographic details, details of ocular examination, and microbiological details were collected. RESULTS: Six patients (10 eyes), with a mean age of 48 + 19.80 years were included. The mean duration of onset of ocular symptoms from the time of diagnosis of COVID was 28.16 + 16.15 days. 8 eyes required surgical intervention, whereas 2 eyes were managed conservatively. Three patients were positive for Candida albicans, two patients were positive for Aspergillus fumigatus, and one patient was a presumed bacterial EE. The majority of the eyes had favorable functional and anatomical outcomes during the post-operative period. CONCLUSION: High-dose corticosteroid therapy in the management of moderate and severe COVID-19 infection may be associated with EE, predominantly fungal.