External limiting membrane angle as a composite predictive index for post-operative ELM closure in full thickness macular holes.

AIM: To evaluate pre-operative qualitative and quantitative parameters of external limiting membranes (ELM) and other associated full thickness macular holes (FTMH) features and their predictive values for post-operative anatomical and functional outcomes. METHODS: This was a retrospective study of 48 eyes that underwent vitrectomy with internal limiting membrane (ILM) peeling for FTMH and had type 1 closure. All subjects underwent optical coherence tomography (SDOCT, Heidelberg, Spectralis), and the eyes were divided into complete ELM closure (CEC) and incomplete ELM closure (IEC) groups based on the post-operative OCTs within 2 months, and ROC curves were used to estimate which of the pre-operative parameters could best predict eyes falling in the CEC group. RESULTS: The mean pre-op ELM defect was smaller in CEC group (594 µm vs 1126 µm, p < 0.001) and so was the pre-op EZ defect (770 µm vs 1186 µm, p = 0.001). The mean ELM angle also was smaller in the CEC group (51.6° vs 102.5°, p < 0.001) and so was the mean hole inlet distance (353 µm vs 596 µm, p < 0.001). The post-operative ELM defect showed a significant negative correlation with visual acuity (r = - 0.319; p = 0.027). The ELM angle was most predictive with an AUROC of 0.958, and a cut-off of 68.3° had a sensitivity of 90% and a specificity of 89%. CONCLUSION: Our study introduces a novel parameter called the ELM angle and proves that it has a high sensitivity and specificity in predicting complete ELM reformation post-surgery in the short term as well as the long term.

Chemical pressure induced spin reorientation in the magnetic structure ofCa3Mn2-xSnxO7(x=0,0.03,0.05).

The effect of partially substituting Tin (Sn) at the Manganese (Mn) site ofCa3Mn2O7, viz.Ca3Mn2-xSnxO7withx=0.03,0.05, on its structural and magnetic properties have been investigated using synchrotron diffraction, neutron diffraction, and bulk magnetization measurements. It is observed that with a substitution ofx=0.03, the minor (≈8%) tetragonal (I4/mmm) structural phase that is present in the predominantly orthorhombic (Cmc21) undopedCa3Mn2O7, completely disappears. The compounds order antiferromagnetically, the ordering temperature decreases with increasing Sn-content, indicating a weakening of the antiferromagnetic exchange interactions. Interestingly, in the ordered state, the spin magnetic moments which were aligned along thea-axis of the unit cell in the undoped compound, are observed to have reoriented with their major components lying in theb - cplane in the Sn-doped compounds. The above influence of Sn-doping is seen to be stemming from a significant modification of the octahedral rotation and tilt mode geometry in the unit cell, that is known to be responsible for driving ferroelectricity in these compounds.

MUTE: A multilevel-stimulated denoising strategy for single cataractous retinal image dehazing.

In this research, we studied the duality between cataractous retinal image dehazing and image denoising and proposed that the dehazing task for cataractous retinal images can be achieved with the combination of image denoising and sigmoid function. To do so, we introduce the double-pass fundus reflection model in the YPbPr color space and developed a multilevel stimulated denoising strategy termed MUTE. The transmission matrix of the cataract layer is expressed as the superposition of denoised raw images of different levels weighted by pixel-wise sigmoid functions. We further designed an intensity-based cost function that can guide the updating of the model parameters. They are updated by gradient descent with adaptive momentum estimation, which gives us the final refined transmission matrix of the cataract layer. We tested our methods on cataract retinal images from both public and proprietary databases, and we compared the performance of our method with other state-of-the-art enhancement methods. Both visual assessments and objective assessments show the superiority of the proposed method. We further demonstrated three potential applications including blood vessel segmentation, retinal image registrations, and diagnosing with enhanced images that may largely benefit from our proposed methods.

Visual Fields in Epidemic Retinitis.

AIM: The aim of the study is to analyze visual fields defects (VFDs) in epidemic retinitis (ER). METHODS: Patients with ER and Humphrey's visual field (HFA) 30-2 performed after resolution were studied. VFD severity grading was performed. Patients treated with oral doxycycline (Group-A) versus doxycycline-steroids (group-B) were compared. RESULTS: Thirty-five eyes of 25 patients were studied. Nasal, inferior, temporal and central VFD were seen in 19 (54.2%), 13 (37.1%), 7 (20%) and 6 (17.1%) eyes, respectively. Grade 0, 1, 2 and 3 VFDs were seen in 4 (11.4%), 15 (42.8%), 12 (34.2%) and 4 (11.4%) eyes respectively. Seven eyes with ≥1 year of follow-up post-resolution also showed grade 0-3 scotomas. Mean severity of scotoma was grade 1.15 (Median: 1) and 1.42 (Median: 1.5) in groups A (n = 13) and B (n = 14), respectively (p = .637). CONCLUSION: ER can cause VFD persisting long after resolution. Treatment with oral doxycycline without steroids was non-inferior to combined treatment with respect to VFD.

Development and persistence of limbic epileptogenesis are impaired in mice lacking progesterone receptors.

Progesterone plays a key role in ovarian cycle-related synaptic plasticity and neuronal excitability. Progesterone receptors (PRs), which mediate the cellular actions of progesterone, are expressed in the hippocampus and other limbic regions, but their functional significance remains unknown. Here, we report a novel role of PRs as crucial mediators in the development of epileptogenesis, which is the process whereby a normal brain becomes progressively epileptic because of precipitating factors. The PR knock-out (PR(-/-)) mouse, which lacks both the PR-A and PR-B isoforms, exhibited an increased resistance to epileptogenesis in the hippocampus and amygdala kindling models. Lack of PRs markedly impaired the persistence of seizure expression at 4 weeks after kindling development. We further show that selective inhibition of PRs in the brain by antisense oligos or pharmacological blockade of PRs by RU-486 [11ß-[p-(dimethylamino)phenyl]-17ß-hydroxy-17-(1-propynyl)estra-4,9-dien-3-one] resulted in a significant decrease in epileptogenesis in wild-type (PR(+/+)) mice. The delayed epileptogenesis in PR knock-out mice was not substantially affected by inhibition of neurosteroid synthesis. Mice lacking PRs show supersensitivity to the antiseizure responses of progesterone. Collectively, these results suggest that PRs in the hippocampus are linked to signaling pathways that control susceptibility to epileptogenesis and possibly persistence of an epileptic-like state. The PR pathway may represent a unique target for preventing or retarding epileptogenesis in females.

Role of perisynaptic parameters in neurotransmitter homeostasis--computational study of a general synapse.

Extracellular neurotransmitter concentrations vary over a wide range depending on the type of neurotransmitter and location in the brain. Neurotransmitter homeostasis near a synapse is achieved by a balance of several mechanisms including vesicular release from the presynapse, diffusion, uptake by transporters, nonsynaptic production, and regulation of release by autoreceptors. These mechanisms are also affected by the glia surrounding the synapse. However, the role of these mechanisms in achieving neurotransmitter homeostasis is not well understood. A biophysical modeling framework was proposed, based on a cortico-accumbens synapse example case, to reverse engineer glial configurations and parameters related to homeostasis for synapses that support a range of neurotransmitter gradients. Model experiments reveal that synapses with extracellular neurotransmitter concentrations in the micromolar range require nonsynaptic neurotransmitter sources and tight synaptic isolation by extracellular glial formations. The model was used to identify the role of perisynaptic parameters on neurotransmitter homeostasis and to propose glial configurations that could support different levels of extracellular neurotransmitter concentrations. Ranking the parameters based on their effect on neurotransmitter homeostasis, nonsynaptic sources were found to be the most important followed by transporter concentration and diffusion coefficient.

Topical interferon therapy in uveitic macular edema.

Purpose: To evaluate efficacy of topical interferon alfa-2b (IFN) in the treatment of uveitic macular edema (UME). Methods: This is a prospective, interventional case study of patients with UME. Injection IFN was reconstituted into eye drops and a four times/day (QID) application was prescribed. Central macular thickness (CMT) on optical coherence tomography (OCT) scan was evaluated. Improvement in CMT by ≥50 µm from the baseline was studied in eyes with presenting CMT ≥400 µm. Results: Twenty eyes of 20 patients with UME were studied: anterior uveitis (n = 3), anterior + intermediate uveitis (n = 5), posterior uveitis (n = 3), retinal vasculitis (n = 3), and panuveitis (n = 6). Mean CMT at the presentation was 423.3 µm (range: 270-604 µm), which improved at 1 month (n = 16), 2 months (n = 10), and ≥3 months (n = 11) follow-up, to 415.3 µm (range: 247-579 µm) (P = 0.411), 364.4 µm (range: 258-566 µm) (P = 0.099), 344 µm (range: 258-484 µm) (P = 0.001), respectively. Twelve eyes of 12 patients had presenting CMT ≥400 µm. In these cases, decrease in CMT by ≥50 µm was seen in 4/10, 4/5, and 5/6 eyes at 1 and 2 months and ≥3 months follow-up. Mean follow-up was 4 months (range: 1-17 months). Complete resolution of UME was seen only in three eyes. No ocular or systemic side effects were observed. Conclusion: Topical IFN therapy in QID doses is safe but may have limited role in UME. Long-term therapy may improve its efficacy. Larger studies with dose modification, combination with other drugs, and with homogeneous uveitis population are recommended.

Epidemic Retinitis with Positive or Negative Weil Felix Test - a Comparative Study and Outcome with Doxycycline.

PURPOSE: To compare clinical manifestations and disease outcomes in Epidemic Retinitis (ER) with positive or negative Weil Felix Test (WFT). METHODS: Retrospective, observational, comparative study. WFT positive or negative patients formed Group 1 and 2, respectively. Patients receiving oral doxycycline monotherapy formed subgroup A and B. Duration of resolution of macular edema and retinitis was compared. RESULTS: Novel finding of "ring retinitis" was observed equally in group 1 and 2. Complete resolution of macular edema took 41.3 days (range: 30-60 days) and 43.68 days (range: 20-105 days) (p = .668) and retinitis lesions resolved in 34.3 days (range: 14-65 days) and 34 days (range: 12-60 days) (p = .875) in group A and B, respectively. All (n = 14) eyes with retinitis within 1 disc diameter of fovea improved better than 20/80 except 1. CONCLUSION: No significant difference with respect to clinical, imaging findings and the treatment outcome was observed in WFT positive or negative cases.

Epidemic retinitis - Factors associated with poor visual outcomes.

PURPOSE: To identify factors other than macular edema and retinitis location responsible for poor visual outcomes in epidemic retinitis (ER). METHODS: A.retrospective, observational, comparative study. Eyes with corrected distant visual acuity (CDVA) 20/200 or worse at resolution formed Group A. Eyes with central macular thickness (CMT) 600 µm or worse and retinitis within 1500 µm to foveal center at the presentation, but improved to CDVA 20/200 or better at the resolution formed Group B. The patient's history, clinical presentation, imaging, and treatment outcomes were studied and the factors responsible for the final visual outcomes were compared in both groups. RESULTS: Groups A and B included 25 eyes each. The mean CDVA at the presentation was 20/400 (range: 20/125-20000) and 20/320 (range: 20/80-20000), and mean CMT at the presentation was 948.5 µm (range: 520-1553) and 912.2 µm (range: 615-1250) in Groups A and B, respectively. All eyes except 1 (Group A) had retinitis lesions within 1500 µm of foveal center. The mean CDVA at the resolution was 20/400 (range: 20/200-20/20000) and 20/40 (range: 20/20-20/80) in Groups A and B, respectively. Older age, male gender, diabetic status, delayed presentation, poor presenting CDVA, bilaterality, presence of keratic precipitates, disk pallor, retinal thinning, and subfoveal deposits had a statistically significant association, whereas the absence of skin rash, ellipsoid zone loss, negative WIDAL, Weil-Felix test, and delayed doxycycline therapy or use of steroids without doxycycline had a statistically insignificant association with poor visual outcomes. CONCLUSION: Apart from presenting CMT and location of retinitis, multiple demographic, clinical, and imaging factors can be implicated for poor visual outcomes.

Intensive topical interferon therapy in uveitic macular edema.

Purpose: To evaluate the efficacy of intensive topical interferon alfa-2b (IFN) therapy in uveitic macular edema (UME). Methods: This is a prospective, interventional case study of eyes with UME. Commercially available injection IFN for subcutaneous use was reconstituted to form eye drops and a dose of 6 times/day for 2 weeks, 5 times/day for next 2 weeks, followed by 4, 3, 2, 1 taper per month was prescribed. Optical coherence tomography (OCT) and clinical examination was done at 0, 2, 4, 8 weeks, and further as required. Results: Nine eyes of 9 patients with UME were studied. Mean central macular thickness (CMT) at presentation was 522.2 µm (range: 408-803 µm). At 2-week, 1-month, and 2-month follow-up, mean CMT decreased to 451.6 µm (range: 322-524 µm), 375.8 µm (range: 287-480 µm), and 360.3 µm (range: 260-485 µm), respectively. Four eyes which showed inadequate response to previous topical IFN therapy (4 times/day) showed significant improvement with intensive therapy at 1 month follow-up. In 4 eyes, UME resolved completely with mean CMT 285.5 µm (range: 260-312 µm) at 7.5 weeks (range: 4-12 weeks). Study exit was seen in 2 cases due to inadequate response and relapse of uveitis. Mean follow up was 3.38 months (range: 1-5 months). Conclusion: Intensive topical IFN therapy can be an alternative therapeutic option in the treatment of UME. Study of intraocular penetration, combination with other drugs, and the efficacy of IFN separately for different uveitic entities may explore new avenues in treatment of UME.

Molecular diffusion model of neurotransmitter homeostasis around synapses supporting gradients.

Neurotransmitter homeostasis in and around a synapse involves complex random processes such as diffusion, molecular binding, and uptake by glial transporters. A three-dimensional stochastic diffusion model of a synapse was developed to provide molecular-level details of neurotransmitter homeostasis not predicted by alternative models based on continuum approaches. The development was illustrated through an example case cortico-accumbens synapse that successfully integrated neuroadaptations observed after chronic cocaine. By incorporating cystine-glutamate exchanger as a nonsynaptic release site for glutamate, the stochastic model was used to quantify the relative contributions of synaptic and nonsynaptic sources to extracellular concentration and to estimate molecular influx rates into the perisynapse. A perturbation analysis showed that among the parameters considered, variation in surface density of glial transporters had the largest effect on glutamate concentrations. The stochastic diffusion model of the example synapse was further generalized to characterize glial morphology by studying the role of diffusion path length in supporting neurotransmitter gradients and isolating the synapse. For the same set of parameters, diffusion path length was found to be proportional to the gradient supported.

SUCCESSFUL SURGICAL OUTCOME OF FULL-THICKNESS MACULAR HOLE WITH CHOROIDAL COLOBOMA.

PURPOSE: To report a case of successful closure of macular hole after surgery in a patient with choroidal coloboma. METHODS: Interventional case report. CASE DESCRIPTION: A 17-year-old boy developed a full-thickness macular hole at the edge of an inferior choroidal coloboma in the right eye. Visual acuity in the right eye was 20/200. Surgical management with 25-G pars plana vitrectomy, internal limiting membrane peeling, and silicone oil tamponade was performed. At 6 weeks after surgery, the macular hole closed with Type 1 closure. After silicone oil removal, the vision in the right eye improved to 20/60. CONCLUSION: Macular hole in the presence of choroidal coloboma is quite uncommon. With better understanding of the etiopathogenesis of macular hole formation and advances in vitreoretinal surgery, it is safe and useful in attempting surgery in these patients.

Epidemic Retinitis with Macular Edema -Treatment Outcome with and without Steroids.

Purpose: To study treatment outcomes with and without oral corticosteroids in epidemic retinitis (ER).Method: A retrospective, observational study of 35 eyes of 29 patients diagnosed as ER. Days taken for resolution of macular edema and retinitis lesions were compared in patients treated with oral antibiotics (Group 1) and with corticosteroids-antibiotics combination (Group 2).Result: Eighteen eyes of 14 patients and 17 eyes of 15 patients formed Groups 1 and 2, respectively. At the presentation, mean best-corrected visual acuity (BCVA) was 40 and 44 letters and mean central macular thickness was 648 (±243) and 626 (±256) microns in Groups 1 and 2, respectively. Macular edema resolved in 30.83 and 31.94 days; retinitis lesions resolved in 36.71 and 41.41 days in Groups 1 and 2, respectively. BCVA improved to 74 and 77 letters in Groups 1 and 2, respectively.Conclusion: ER with macular edema can be well managed without corticosteroids.

Choroidal Thickness in Multifocal Dendritic and Placoid Serpiginous-Like Choroiditis: A Comparative Study.

BACKGROUND AND OBJECTIVE: To study spectral-domain optical coherence tomography (SD-OCT) characteristics in multifocal advanced dendritic serpiginous-like choroiditis (D-SLC) and placoid serpiginous-like choroiditis (P-SLC). PATIENTS AND METHODS: Retrospective, comparative study. SD-OCT features were studied in both the groups. Area of involvement (AoI) due to SLC lesions was calculated, and cases with comparable AoI from both the groups were subclassified into Group A (subgroup D-SLC) and Group B (subgroup P-SLC). Central choroidal thickness (CT) was measured, and comparative analysis was performed. RESULTS: Thirty-four eyes (15 D-SLC, 19 P-SLC) of 28 patients were studied. Mean AoI for Group A (n = 10) and for Group B (n = 12) was 197,066.50 units (range: 139,602 to 267,151 units) and 203,407.33 units (range: 148,156 to 285,048 units), respectively (P = .553). Mean central CT was 217.92 µm for DSLC and 152 µm for P-SLC (P = .01). CONCLUSIONS: The choroid was significantly thinner at the resolution in P-SLC than in D-SLC form. P-SLC renders more choroidal destruction and may warrant aggressive treatment. [Ophthalmic Surg Lasers Imaging Retina. 2021;52:438-442.].

Telepsychiatry and Addiction Treatment.

The need and the importance of telemedicine has been brought to the forefront during the ongoing pandemic of COVID-19. It has created another viable option for treatment delivery while reducing risks. However, there are major concerns regarding the delivery of services for treatment of substance use disorders using telepsychiatry. We discuss the various concerns and opportunities, the different international practices, and the Indian guidelines. We believe that there needs to be a balance between access to treatment and medication with reasonable checks and call for more patient and provider friendly practices. We also propose certain modifications in the Indian Telepsychiatry Guidelines.

Plume Sign in the Deturgescence of Macular Cysts - A Novel OCT Finding.

AIM: To describe a novel OCT finding called "Plume sign" in macular cysts. METHODS: Case records of five cases were retrospectively reviewed. Their case history and imaging findings on spectral domain optical coherence tomography (SD-OCT, Spectralis, Heidelberg, Germany) have been described. RESULTS: We observed five cases which had a solitary cyst foveal or parafoveal in location, was unique due to the presence of a plume-shaped internal substance, was treated with topical NSAIDs and was associated with good visual outcomes. We observed three cardinal events; firstly, retinal thickening followed by the formation of a foveal or parafoveal solitary cyst. Secondly, a vertical expansion of the solitary cysts in an inverted flask-shaped configuration associated with splitting of the retinal layers suggested by a hyper-reflective line and/or a hyporeflective cleft in the outer nuclear layer. Thirdly and finally, a breach of the outer retina with involvement of the external limiting membrane (ELM) and ellipsoid zone (EZ) with an exit trail of proteinaceous material through the defect in the shape of a plume of smoke hyper-reflective on OCT followed by deturgescence of the cyst. CONCLUSION: In conclusion, we describe the "plume" sign - a novel OCT finding is cysts and provide a possible pathogenic hypothesis.

Retinal vasospastic phenomenon in a known case of systemic lupus erythematosus.

Retinal vasospasm was visualized in a young female; a known case of systemic lupus erythematosus (SLE) retinopathy with unaffected vision. The fundus fluorescein angiogram showed a cyclical filling and emptying of the retinal vessels which was suggestive of vasospasm and a retinal Raynaud's-like phenomenon with no obvious perfusion deficit. There was retinal thinning involving the superficial layers that was seen on optical coherence tomography (OCT), capillary fill voids on OCT angiography, and retinal surface undulations seen on multicolor imaging. All imaging was performed on Spectralis (Heidelberg, Germany).

A Long-Term Follow-up of Retinal Vasculitis - Do They Develop Systemic Disease?

Purpose: To study systemic association and relapses in a long-term follow-up of primary retinal vasculitis (PRV) and possible tubercular vasculitis (PTV) cases. Method: Retrospective, descriptive chart review of patients diagnosed as PRV and PTV with ≥1-year follow-up. Clinical presentation, systemic association, morphology of vasculitis, relapses, and treatment were noted. Results: 123 eyes of 76 patients were studied. Occlusive (n = 97), exudative (n = 16), combined (n = 10) and focal (n = 7) vasculitis were seen. Vitreous hemorrhage at presentation was noted in 27% eyes (n = 33). Four patients (3.25%) developed systemic disease during follow-up (2 psoriasis, 1 Systemic Lupus Erythematosus, 1 ulcerative colitis). Mean number of cases with relapses were 45 (59.21%). Number of cases with relapses in PRV and PTV were 20 (66.66%) and 16 (66.66%), respectively. (p = 1) Conclusion: Systemic disease attributed to vasculitis can rarely develop during follow up of PRV and PTV patients. Relapses remain almost same in PTV and PRV.

Serpiginous-Like Choroiditis (SLC) - Morphology and Treatment Outcomes.

PURPOSE: To study morphology and treatment outcomes in serpiginous-like choroiditis (SLC). METHODS: A retrospective chart review of SLC cases with ≥1-year follow-up. SLC lesions with elongated borders, thin body named dendritic (D-SLC), large lesions still with elongated borders named advanced dendritic (AD-SLC), and lesions with rounded borders, thick body called placoid (P-SLC). History, investigations, treatment response, and relapses were studied. RESULTS: Thirty-three eyes [D-SLC (n = 14), AD-SLC (n = 13), P-SLC (n = 6)] of 24 patients were studied. Resolution on Fundus autofluorescence achieved at 8.6 months (Range: 4-12 months). 0/16 eyes treated with anti-tubercular therapy (ATT) and 4/11 eyes treated without ATT had at least one recurrence in (D-SLC + AD-SLC) group (p = .019). Mean best corrected visual acuity at final follow-up was 20/20, 20/25, and 20/60 in D-SLC, AD-SLC, and in P-SLC, respectively. CONCLUSION: P-SLC has poor visual prognosis compared to AD-SLC and D-SLC. ATT may prevent recurrences in D-SLC and AD-SLC.