Assemble-Disassemble-Reassemble Dynamics in Copper Nanocluster-Based Superstructures.

Assembling metal nanoclusters (MNCs) to form superstructures generates exciting photophysical properties distinct from those of their discrete precursors. Controlling the assembly process of MNCs and understanding the assembly-disassembly dynamics can have implications in achieving the reversible self-assembly of MNCs. The formation of self-assembled copper nanoclusters (CuNCs) as homogeneous superstructures and the underlying mechanisms governing such a process remain unexplored. Smart molecular imprinting of surface ligands can establish the forces necessary for the formation of such superstructures. Herein, we report highly luminescent, ordered superstructures of 4-phenylimidazole-2-thiol (4-PIT)-protected CuNCs with the help of l-ascorbic acid as a secondary ligand. Through a comprehensive spectroscopic analysis, we deciphered the mechanism of the self-assembly process, where the role of interligand H-bonding and C-H-π interactions was established. Notably, efficient reversibility of assembly-disassembly was demonstrated by re-establishing the interligand interactions and regenerating their photophysical and morphological signatures.

In Situ Crystallization, Differential Growth, and Multicolor Emission of Silver Nanoclusters.

The real-time monitoring of the stepwise growth process of the molecular crystal reveals a conclusive understanding of the morphological evolution, which otherwise remains elusive during the conventional crystallization processes. Herein, we report the in situ crystallization of silver nanoclusters (AgNCs) with special emphasis on their differential growth and multicolor emissive properties. A subtle variation of the methanol (MeOH) proportion in the reaction mixture induces the differential growth of these AgNCs, and thereby, a dramatic modulation in their optical properties was observed. Additionally, by increasing the temperature of the reaction (from a low temperature ice bath to 25 °C), an uncontrolled formation of AgNCs along with metallic silver nanoparticles (AgNPs) was observed, which was primarily induced by accelerating the reaction kinetics. We hope that this investigation comprehensively uncovers the serious bottlenecks of the conventional crystallization processes by showcasing systematic monitoring of structural evolution to the higher-ordered crystalline state.

pH-Switchable phenylalanine-templated copper nanoclusters: CO2 probing and efficient peroxidase mimicking activity.

Inter-cluster conversion through the strategic tuning of external stimuli and thereby modulation of the optical properties of metal nanoclusters (MNCs) is an emerging domain for exploration. Herein, we report the preparation of blue-emitting CuNCs using phenylalanine (Phe) as a template under acidic conditions (pH ∼ 4). The as-prepared CuNCs exhibit a sequential tuning of the photophysical properties upon varying the pH of the solution from pH ∼4 to pH ∼12. Blue-emitting CuNCs (B-CuNCs, λem = 410 nm) are systematically converted to cyan-emitting CuNCs (C-CuNCs, λem = 490 nm) with a large red-shifted emission maximum by 80 nm as a function of pH. Our present investigation delineates an unprecedented switchability of the photoluminescence (PL) properties of the CuNCs with the variations of the pH from pH ∼4 to pH ∼12. Both the Phe-templated CuNCs (B-CuNCs and C-CuNCs) were broadly characterized by various spectroscopic and morphological techniques. The X-ray photoelectron spectroscopy (XPS) studies reveal the presence of different oxidation states in the metallic core of B-CuNCs and C-CuNCs. These results in turn substantiate the pH-induced intercluster conversion of CuNCs through the substantial change in their core composition as well as valence states. Owing to the pH sensitivity, the CuNCs act as an efficient and highly sensitive probe for CO2, and quantitative estimation of the dissolved CO2 in the form of bicarbonate ions has been achieved through the enhancement of the PL intensity, wherein a very low value of the limit of detection (LOD) of ∼60 µM was obtained. Furthermore, we demonstrated that the CuNCs act as an efficient bio-catalyst with peroxidase mimicking enzymatic activity which has been investigated using OPD as a substrate under physiological conditions (pH ∼7.4 and temperature ∼37 °C). The mechanistic investigations confirmed that the oxidation of OPD mainly proceeds through the generation of hydroxyl radicals (˙OH). We hope the present investigations shed light on a multidimensional aspect of MNCs and uncover an upsurging recent interest in MNCs to act as an artificial enzyme.

Fluorescence Resonance Energy Transfer in a Supramolecular Assembly of Luminescent Silver Nanoclusters and a Cucurbit[8]uril-Based Host-Guest System.

The understanding of interactions between organic chromophores and biocompatible luminescent noble metal nanoclusters (NCs) leading to an energy transfer process that has applications in light-harvesting materials is still in its nascent stage. This work describes a photoluminescent supramolecular assembly, made in two stages, employing an energy transfer process between silver (Ag) NCs as the donor and a host-guest system as the acceptor that can find potential applications in diverse fields. Initially, we explored the host-guest chemistry between a cationic guest ethidium bromide and cucurbit[8]uril host to modulate the fluorescence property of the acceptor. The host-guest interactions were characterized by using UV-vis absorption, steady-state and time-resolved spectroscopy, molecular docking, proton 1H nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and isothermal calorimetry studies. Next, we prepared a series of blue-emitting AgNCs using different templates such as proteins and peptides. We have found that these AgNCs can be employed as a donor in the energy transfer process upon mixing with the above acceptor for emission color tuning. Our in-depth studies also revealed that surface ligands could play a key role in modulating the energy transfer efficiency. Overall, by employing a noncovalent strategy, we have tried to develop Förster resonance energy transfer (FRET) pairs using blue-emitting NCs and a host-guest complex that could find potential applications in constructing advanced sustainable light-harvesting, white light-emitting, and anti-counterfeiting materials.

Human immunodeficiency virus retinopathy with presumed cytomegalovirus retinitis with macular oedema in a diabetic.

A man in his early 50s on regular follow-up for a stable non-proliferative diabetic retinopathy (NPDR) presented with decreased vision, worsening of retinal pathology and macular oedema in both eyes. His corrected distance visual acuity (CDVA) was 6/9 in the right eye and 6/15 in the left eye and fundus examination showed multiple intraretinal haemorrhages in all quadrants. His systemic workup revealed a severe thrombocytopaenia, which prompted a further detailed systemic evaluation revealing him to be positive for HIV with retinopathy complicating the pre-existing NPDR. Given the significant inflammation and macular oedema, a cocktail of intravitreal bevacizumab, ganciclovir and dexamethasone was administered. The retinopathy and macular oedema resolved and the CDVA improved to 6/6 in both eyes over a 6-month follow-up period. Any sudden worsening of fundus findings in a patient with diabetes necessitates immediate and detailed ocular and systemic evaluation, especially when the immune status is unknown.

Characteristics of retinal pigment clumps in Type 2 macular telangiectasia (MacTel).

OBJECTIVE: To assess the relationship of retinal pigment clump (RPC) size and its location with visual acuity and retinal neovascularisation in eyes with type 2 macular telangiectasia (MacTel). METHODS: In this cross-sectional study, eyes diagnosed with type 2 MacTel showing RPC were included. Area occupied by pigment was measured on the multicolour image using the area tool on the Spectralis, Heidelberg machine. Pigment location within retinal layers was noted with OCT. Analysis was performed to identify factors associated with poor vision and proliferative disease. RESULTS: Sixty-two eyes of 42 patients diagnosed with type 2 MacTel and RPC were included. The mean age was 64.31 ± 10.19 years. There were 13 (31%) males and 29 (69%) females in the study. 74% of patients were diabetics and the mean logMAR visual acuity of the participants was 0.619 ± 0.359. Univariate and multivariate binary logistic regression analysis identified female gender (p = 0.026), increasing RPC size (p = 0.008) and its presence above the outer plexiform layer (p = 0.006) to be associated with poor vision and proliferative disease in type 2 MacTel. CONCLUSION: Our data identified female gender, larger pigment size and its location above the OPL to be associated with poor vision and proliferative disease. This data may be useful for further improving the current system for staging disease severity in type 2 MacTel.

DIRECT LASER PHOTOCOAGULATION TO THE DILATED RIGHT-ANGLED VESSEL IN THE MANAGEMENT OF PROLIFERATIVE TYPE 2 MACULAR TELANGIECTASIA.

PURPOSE: To report a case of proliferative Type 2 macular telangiectasia treated successfully with direct laser photocoagulation to the right-angled vessel. METHODS: Descriptive case report. CASE DESCRIPTION: A 61-year-old man, with no past medical history, was diagnosed and treated previously elsewhere for bilateral proliferative Type 2 macular telangiectasia. He complained of recent onset decrease in vision in his right eye for last 2 months. Right eye visual acuity was counting fingers at 3 m and left eye was 6/18. Fundus examination showed proliferative Type 2 macular telangiectasia in both eyes with active neovascular complex in the right eye. Direct thermal laser photocoagulation to the tips of the right-angled vessels with single-spot PASCAL Synthesis (Topcon Medical Laser System) at 532 nm wavelength was done. After laser, reduction in the hyporeflective space height was noted on optical coherence tomography. No additional intravitreal anti-vascular endothelial growth factor injections were required. At the last 6-months follow-up visit, visual acuity improved to 6/36, N18 in the right eye. CONCLUSION: Direct laser photocoagulation to the right-angled vessel can be considered as possible treatment option for proliferative Type 2 macular telangiectasia, especially in patients nonresponsive to anti-vascular endothelial growth factor therapy. However, long-term follow-ups are required to see whether it is possible to maintain the efficacy.

Choroidal Melanocytic Hamartoma.

We report on a case series that revealed flat, choroidal lesions on optical coherence tomography (OCT) and on enface MultiColor® (MCI) imaging of the fundus but were not noticeable on clinical examination or conventional color fundus images. This observational study included 12 eyes from 11 patients who had distinct, orange-colored lesions on MCI. Retinal imaging was conducted using conventional color fundus photography and OCT. On the color fundus images and the blue and green reflectance channels of MCI, each of the lesions was difficult to distinguish. On the infrared channel, the lesion was identified as bright white in color and bright orange on the multicolor image. The lesion was identified on OCT as a flat, homogeneous hyperreflective lesion involving the choroid, with an intact overlying retinal pigment epithelium and retinal layers. A comparison of the clinical and imaging features with other known entities led to the conclusion that the lesion was a distinct clinical entity. The presence of melanin in the lesion was confirmed based on the retinal imaging findings and the light absorption properties of melanin. As a result, the lesion was named as 'choroidal melanocytic hamartoma'. A longer follow-up is required to confirm the benign nature of this clinical entity.

Unilateral Endogenous Bacterial Endophthalmitis Post-Coronavirus Disease-19 in an Healthy Asian Indian Male.

Coronavirus disease 2019 (COVID-19) is associated with ocular involvement either during or after the infection. These include conjunctivitis, conjunctival hyperemia, chemosis, epiphora, reactivation of anterior uveitis, or presenting as anterior sclero-uveitis, cotton wool spots, retinal hemorrhages, retinal artery/vein occlusion, ophthalmic artery occlusion, panuveitis, papillophlebitis, central serous retinopathy, presumed fungal endophthalmitis, and multifocal chorioretinitis. A 47-year-old Asian Indian male was diagnosed with COVID-19 and had no other systemic history of note at the time of admission. Three weeks later, he developed sudden loss of vision in the right eye (OD). Visual acuity in OD was perception of light. OD had features of endophthalmitis. OD underwent pars plana vitrectomy with intravitreal antibiotics. Anterior chamber tap for fungal culture and polymerase chain reaction for panfungal genome was negative. Culture of ocular specimens did not reveal bacterial growth. Vitreous sample showed few Gram-positive cocci in singles and pairs with no evidence of fungal elements. Polymerase chain reaction for eubacterial genome was positive. He was treated with topical and systemic antibiotics and steroids. Final follow-up 6 weeks later, OD had a best-corrected visual acuity which was 20/200 with a quiet anterior chamber, cataract, with a macular traction and reduced sub retinal exudates and fluid. Post-COVID-19 sequelae causing sight-threatening manifestations as illustrated by this case report needs early recognition and prompt treatment to achieve a favorable visual outcome.

Choroidal and retinal thickness variations in ocular albinism.

Purpose: To study the retinal and choroidal thickness variations on enhanced depth imaging optical coherence tomography scans in ocular albinism (OA) and compare with age-matched healthy subjects. Methods: This retrospective observational study had 48 eyes of 24 patients diagnosed clinically as OA and age, sex, and axial length-matched control healthy subjects. All patients underwent detailed ophthalmic examination and a single-line horizontal-raster enhanced depth imaging - optical coherence tomography scan (Spectralis, Heidelberg Engineering). Retinal and choroidal thickness was measured, compared, and analyzed between the two groups. Mann-Whitney U test was used for analysis between the two groups. P < 0.05 was considered significant. Results: The mean age was 28.3 ± 11.6 and 29.9 ± 10.6 years in the OA group and control group, respectively. Spherical equivalents ranged from -8.5D to +10.5D in the OA group and from -8.0D to +10.0D in the control group. The mean axial length between the two groups (P = 0.652) were comparable. The average retinal thickness (272 ± 34.3 vs. 213 ± 13.8 µm; P < 0.001) was greater in the OA group as compared to controls. The mean choroidal thickness (184 ± 78.4 vs. 287 ± 46.4 µm; P < 0.001) was significantly thinner in the OA group. Conclusion: Acquisition of OCT scans in OA can be challenging. This study showed that the subfoveal retinal thickness and choroidal thickness measured across the scans were significantly different in the OA group compared to controls. In the future, more studies are required to evaluate the role of the choroid and its relationship to emmetropization in albinism.

Diabetic Retinopathy and Diabetic Macular Edema in People With Early-Onset Diabetes.

This study examined the clinical profile, treatment profile, and vision outcomes of people ≤40 years of age with diabetes and diabetic macular edema (DME). Within this age-group, the prevalence of center-involving DME was 16%, with 74% of eyes showing cystoid edema, 37% showing spongiform edema, and 41% having neurosensory detachment. Longer diabetes duration (P = 0.001) and greater severity of diabetic retinopathy (P <0.001) were associated with DME prevalence. Thus, regular and more frequent follow-up, as well as early and aggressive treatment of diabetic eye disease, are required in people diagnosed early with diabetes.

Macrocyclic Cavitand ß-Cyclodextrin Inhibits the Alcohol-Induced Trypsin Aggregation.

Trypsin, the most abundant pancreatic protein, aids in protein digestion by hydrolysis and exhibits aggregation propensity in presence of alcohol, which can further lead to pancreatitis and eventually pancreatic cancer. Herein, by several experimental and theoretical approaches, we unearth the inhibition of alcohol-induced aggregation of Trypsin by macrocyclic cavitand, ß-cyclodextrin (ß-CD). ß-CD interacts with the native protein and shows inhibitory effect in a dose dependent manner. Moreover, the secondary structures and morphologies of Trypsin in presence of ß-CD also clearly emphasize the inhibition of fibril formation. From Fluorescence Correlation Spectroscopy, we observed an enhancement in diffusion time of Nile Red with ∼2.5 times increase in hydrodynamic radius, substantiating the presence of fibrillar structure. Trypsin also shows reduction in its functional activity due to alcohol-induced aggregation. Our simulation data reports the probable residues responsible for fibril formation, which was validated by molecular docking studies.

Spectral domain OCT features in type 2 macular telangiectasia (type 2 MacTel): its relevance with clinical staging and visual acuity.

BACKGROUND: To report spectral domain optical coherence tomography (SDOCT) imaging findings in type 2 macular telangiectasia (MacTel) and correlate them with clinical stages and visual acuity. METHODS: This retrospective, cross-sectional study included type 2 MacTel cases who underwent SDOCT imaging with Spectralis machine. Macular SDOCT images were analysed. Imaging features were tested for correlation with different clinicals stages and visual acuity. RESULTS: 212 eyes of 108 type 2 MacTel patients were included. Hyperreflective middle retinal layer (87%) was the most frequently detected abnormality. This was followed by inner retinal cavities (49%), outward bending of inner retinal layers (35%), retinal pigment clumps (35%) and foveal contour irregularity (31%). Hyperreflective middle retinal layers (p < 0.001), inner (p = 0.032) and outer retinal (p = 0.002) cavities and internal limiting membrane drape (p = 0.031) were associated with poor vision in non-proliferative group and presence of retinal pigment clumps (p = 0.002), subretinal fluid (p = 0.037) and foveal contour irregularity (p < 0.001) were associated with poor vision in proliferative group. CONCLUSION: The described SDOCT features are practical for the diagnosis and staging in type 2 MacTel. Presence of hyperreflective middle retinal layers, hyporeflective inner and outer retinal cavities and internal limiting membrane drape were associated with poor vision in the non-proliferative group while retinal pigment clumps and subretinal neovascular membrane were associated with proliferative group and poor vision. Further long-term studies are required to describe the progressive and sequential changes on SDOCT.

Contributory factors for developing foveal neovascularization in proliferative diabetic retinopathy.

PURPOSE: Foveal neovascularisation (NV) in proliferative diabetic retinopathy (PDR) is uncommon. The study aim is to analyse a series of cases of foveal NV in PDR and ascertain the factors leading to its development. METHODS: In this retrospective case-control study, optical coherence tomography (OCT) and OCT-angiography (OCTA) images of PDR cases with/without foveal NV diagnosed on fluorescein angiography were analysed. RESULTS: From 124 consecutive PDR eyes, foveal NV was identified in 12 (10%) eyes. Eyes with foveal NV showed thin choroid (p = 0.001), increased FAZ area and reduced vessel density at the macula compared to control group on OCT and OCTA. After regression analysis, an increased FAZ in the superficial capillary plexus slab (p = 0.002) was associated with foveal NV development. CONCLUSION: Our case series suggest that foveal NV is an uncommon finding, occurring due to reduced choroidal and inner retinal perfusion at the macula. Further studies are required to assess the treatment outcomes in such eyes.

Visual function correlates with foveal slope, retinal and choroidal thickness on optical coherence tomography in type 2 Macular Telangiectasia.

PURPOSE: To correlate the foveal slope angle (FSA), retinal (RT) and choroidal (CT) thickness measured using optical coherence tomography (OCT) across different stages of type 2 macular telangiectasia (MacTel) with best-corrected visual acuity (BCVA). METHODS: A cross-sectional study of 182 gradable quality macular OCT images of 49 patients with type 2 MacTel was carried out. RT was measured on the Spectralis OCT machine from ETDRS (Early Treatment Diabetic Retinopathy Study) retinal thickness map and later used for calculating FSA. RT and CT were measured at 500-µm intervals up to 1500 µm from foveal centre manually. The change in RT, CT and FSA across five stages of type 2 MacTel was assessed. The measurements were correlated with BCVA. RESULTS: The FSA, RT and CT were calculated quadrantwise and stagewise. The FSA and RT showed a significant negative correlation with disease stage and BCVA (p < .05) in all four quadrants. No significant correlation was noted between CT and BCVA. Multivariate linear regression analysis identified the temporal FSA to correlate best with BCVA. CONCLUSION: BCVA correlates best with temporal FSA. Smaller the temporal FSA, poorer the vision.

Bacillary layer detachment in acute nonpenetrating ocular trauma.

OBJECTIVE: To study the clinical and visual outcomes of patients presenting with bacillary layer detachment (BLD) on optical coherence tomography (OCT) in blunt ocular trauma. DESIGN: Retrospective observational study. PARTICIPANTS: Clinical fundus photographs and OCT scans with Spectralis machine were reviewed to identify patients with blunt ocular trauma showing BLD. METHODS: Patients were further analyzed for changes in their anatomic features such as subretinal hemorrhage, intrabacillary layer bleed. subretinal fibrosis and choroidal rupture and reattachment of BLD, and visual outcomes over subsequent follow-up visits. RESULTS: Of a total of 77 eyes with blunt ocular trauma, 6 (8%) eyes with BLD were identified. All patients were male with presenting visual acuity ranging from 6/9 to 2/60 (mean logMAR = 1.119; Snellen's equivalent = 20/263). The time interval between trauma and presentation ranged from 1 to 7 days. Subretinal hemorrhage and choroidal rupture were noted in all 6 eyes. On OCT, foveal involvement by the BLD was noted in 5 eyes. Intrabacillary layer hemorrhage was noted in all patients. Reattachment of the bacillary layer and visual acuity improvement were noted in all eyes at the final visit. The time interval for resolution of BLD ranged from 2 to 10 days. Visual acuity of 6/36 or less was secondary to subretinal fibrosis close to the fovea and subfoveal choroidal rupture. CONCLUSION: BLD in blunt ocular trauma is a rare finding, shows complete resolution, and appears not to influence visual or anatomic outcome.

The preproliferative stage in type 2 macular telangiectasia (MacTel type 2).

PURPOSE: To study clinical and imaging features of various stages of macular telangiectasia (MacTel type 2). METHODS: In this retrospective study, cases of MacTel type 2 with fluorescein angiography (FA), optical coherence tomography (OCT) and OCT-angiography (OCTA) imaging were included. Based on angiographic perifoveal fluorescence, two groups were formed: group 1: diffuse hyperfluoroscence and group 2: diffuse + focal hyperfluoroscence. Later, based on OCT features, group 2 was subdivided into group 2A: without SRNVM and group 2B: with SRNVM. Clinical, FA, OCT and OCTA features were analysed. Eyes showing conversion to the proliferative stage at final visit were noted. RESULTS: Ninety-four eyes of 48 patients were included. Group 1 (n = 28) showed diffuse perifoveal hyperfluoroscence, hyperreflective middle retinal layers, absent SRNVM (p = 0.006) on OCT and dilated perifoveal capillaries in deep capillary plexus (DCP) on OCTA. Group 2A (n = 40) showed diffuse + focal perifoveal hyperfluoroscence, hyperreflective middle retinal layers (p = 0.001), hyporeflective outer retina cavities (p = 0.021), absent SRNVM with dilated and bunching perifoveal capillaries (p = 0.004) in DCP. Group 2B (n = 26) showed late diffuse + focal perifoveal hyperfluoroscence, foveal contour irregularity (p = 0.002), retinal pigment clumps (p = 0.015) and SRNVM on OCT with bunching of capillaries in DCP and vessels in outer retina (p = 0.002). Five eyes showed conversion to group 2B at final visit. CONCLUSION: There exists a distinct disease stage called "preproliferative" MacTel type 2 showing clinical features of non-proliferative disease, diffuse + focal perifoveal hyperfluoroscence on FA, absent SRNVM on OCT and bunching perifoveal capillaries in DCP on OCTA. Its identification is important for suspecting proliferative disease, planning management and follow-up visit accordingly.

Functional relevance of macular telangiectasia (MacTel) area on multicolour imaging in type 2 MacTel.

PURPOSE: To analyse the correlation between area of macular telangiectasia (MacTel) involvement on multicolour (MC) imaging, disease stages and visual acuity in type 2 MacTel. METHODS: In this retrospective analysis of MC images, confirmed cases of type 2 MacTel were graded into different disease stages as per Gass and Blodi and Yannuzzi et al classification systems. The 'MacTel area' was calculated by marking the outer boundary of an area with abnormally increased reflectivity to confocal blue wavelength light. At every follow-up visit, best-corrected visual acuity, MacTel area and stage of disease on the MC image was documented. Analyses between disease stage, MacTel area and visual acuity was carried out. RESULTS: In total, 92 eyes of 49 patients were included in the study. The mean age was 59.6 ± 8.96 years. About 182 high-quality gradable MC images were available for analysis. There was a statistically significant difference in the visual acuity (p < 0.001) and area of involvement (p < 0.001) in the non-proliferative and proliferative type 2 MacTel groups. An increase in disease severity stage statistically correlated positively with Mactel area (r = 0.544; p < 0.001) and logMAR visual acuity (r = 0.329; p < 0.001). Over time, there was a significant increase in area of MacTel involvement (p = 0.012) with an associated decrease in the visual acuity (p = 0.023). CONCLUSION: The MacTel area measured on MC imaging showed a strong positive correlation with disease stage and a negative correlation with visual acuity. This could serve as a useful biomarker in clinical trials and understanding the natural history of the disease.