Comparative genomics uncovers the evolutionary history, demography, and molecular adaptations of South American canids.

The remarkable radiation of South American (SA) canids produced 10 extant species distributed across diverse habitats, including disparate forms such as the short-legged, hypercarnivorous bush dog and the long-legged, largely frugivorous maned wolf. Despite considerable research spanning nearly two centuries, many aspects of their evolutionary history remain unknown. Here, we analyzed 31 whole genomes encompassing all extant SA canid species to assess phylogenetic relationships, interspecific hybridization, historical demography, current genetic diversity, and the molecular bases of adaptations in the bush dog and maned wolf. We found that SA canids originated from a single ancestor that colonized South America 3.9 to 3.5 Mya, followed by diversification east of the Andes and then a single colonization event and radiation of Lycalopex species west of the Andes. We detected extensive historical gene flow between recently diverged lineages and observed distinct patterns of genomic diversity and demographic history in SA canids, likely induced by past climatic cycles compounded by human-induced population declines. Genome-wide scans of selection showed that disparate limb proportions in the bush dog and maned wolf may derive from mutations in genes regulating chondrocyte proliferation and enlargement. Further, frugivory in the maned wolf may have been enabled by variants in genes associated with energy intake from short-chain fatty acids. In contrast, unique genetic variants detected in the bush dog may underlie interdigital webbing and dental adaptations for hypercarnivory. Our analyses shed light on the evolution of a unique carnivoran radiation and how it was shaped by South American topography and climate change.

Pigmentation abnormalities in Coffin-Siris syndrome.

Pigmentary abnormalities in Coffin-Siris Syndrome should be considered as part of the wide phenotypical spectrum of this patients.

Intravitreal acetazolamide implant for pseudophakic cystoid macular edema.

BACKGROUND: Pseudophakic cystoid macular edema (PCME) is the most common cause of visual acuity deterioration after uncomplicated cataract surgery. There is no consensus regarding how to manage recurrent or refractory cases. REPORT: A 54-year-old woman complained of decreased vision and central metamorphopsia in the right eye (OD) 3 months after uneventful cataract surgery. Visual acuity was 0.3 logMAR (20/40) OD and 0.1 logMAR (20/25) OS. Reduced macular brightness was seen OD on funduscopy associated with increased macular thickness on optical coherence tomography (OCT). Pseudophakic cystoid macular edema (PCME) was diagnosed, and treatment with oral acetazolamide was tried without success. The patient underwent a single intravitreal injection of an acetazolamide implant (260 µg) OD as off-label treatment. Four weeks following the injection, she reported complete resolution of her metamorphopsia and visual loss OD. Four months later, her visual acuity was 0.0 logMAR (20/20) in OD and 0.1 logMAR (20/25) in OS. The patient reported no discomfort after the injection procedure. Laboratory and ophthalmologic tests did not identify any adverse effects of the medication. CONCLUSION: We show that PCME refractory to conventional treatment improved after intravitreal acetazolamide implant injection. Further investigation is warranted to confirm these preliminary findings.

Safety of intravitreal metoprolol in eyes with central serous chorioretinopathy.

PURPOSE: To investigate ocular safety of intravitreal metoprolol in eyes with central serous chorioretinopathy. METHODS: Five eyes of five patients diagnosed with chronic central serous chorioretinopathy (cCSC) previously treated unsuccessfully with oral spironolactone, micropulse laser and intravitreal anti-vascular endothelial growth factor agents were enrolled and received off-label intravitreal metoprolol (50 µg/0.05 ml). Baseline and follow-up examinations included measurement of best-corrected visual acuity (BCVA), intraocular pressure, anterior chamber cellular/flare scores, vitritis classification, fluorescein and indocyanine green angiography, spectral domain optical coherence tomography and electroretinography (ERG), recorded by means of DTL electrodes and following the standard suggested by the International Society for Clinical Electrophysiology of Vision (ISCEV). The total follow-up period was 4 weeks. RESULTS: There were no significant differences between baseline and follow-up ERG parameters: scotopic or photopic, a- and b-wave amplitude and implicit time, nor oscillatory potentials amplitude, or whatsoever. No intraocular inflammation sign was observed. In addition, BCVA showed small improvement in 4 or kept baseline values in 1 patient. The subretinal and/or intraretinal fluid volume reduced in all patients at 1 month after treatment. CONCLUSION: Patients with refractory cCSC treated with intravitreal 50 µg/0.05 ml metoprolol showed no signs of acute ocular toxicity, along with intraretinal fluid reduction and slight BCVA improvement 1 month after injection. This data suggest that intravitreal metoprolol may be a safe alternative for cCSC.

Effect of extended light activation and increment thickness on physical properties of conventional and bulk-filled resin-based composites.

OBJECTIVES: To evaluate the biaxial flexural strength (BFS), flexural modulus (BFM), and Knoop microhardness (KHN) of incremental and bulk-filled resin-based composites (RBCs) using extended curing exposure times. MATERIALS AND METHODS: Disc specimens (n = 8; 6-mm diameter) were fabricated using three stacked molds (0.5-mm thick for the top and bottom molds, and a 1-mm-thick center mold for the conventional and 3-mm thick for the bulk-fill RBCs). Conventional (Tetric EvoCeram/TCE and Filtek Z250/FIZ) and bulk-fill RBCs (Tetric EvoCeram Bulk Fill/TBF and Filtek One Bulk Fill Restorative/FOB) were evaluated. The stacked RBC-filled molds were light-cured for (1) the manufacturer-recommended exposure (MRE) duration; (2) 50%, and (3) 100% extension of the MRE. The BFS, BFM, and KHN of the top and bottom discs were measured. BFS and BFM were analyzed by three-way ANOVA (material*curing time*depth) and Tukey's post hoc (α = 0.05). KHN was analyzed by two-way ANOVA (curing time*depth) and Tukey's post hoc (α = 0.05). RESULTS: Extending the exposure duration did not change the BFS and BFM on the top of the RBCs, but the BFS and KHN increased at the bottom of bulk-fill RBCs. For the conventional RBCs, TCE showed the highest increase on BFS at the bottom, going from 53.6 MPa at T1 to 69.9 at T3. Among the bulk-fill RBCs, FOB presented the highest increase on the bottom BFS (T1: 101.0 ± 19.9 MPa, T3: 147.6 ± 12.9 MPa). For all RBCs and exposure times, BFS and KHN were lower at the bottom. Only FIZ and FOB reached a bottom-to-top hardness ratio of 80%, at T3 and T2. CONCLUSION: A significant increase on the BFS and KHN on the bottom of bulk-fill RBCs can be observed when the time of exposure to the curing light is double the MRE. However, extended exposure does not eliminate differences on the BFS and KHN between the shallow and deep regions of RBCs. TCE and TBF failed to reach an acceptable B/T hardness ratio at all evaluated exposure times. CLINICAL RELEVANCE: Mechanical properties of RBCs can be affected by insufficient polymerization, specially at deeper regions of the increment. Therefore, clinicians should consider applying twice the MRE to curing-light to polymerize the maximal increment thickness of bulk-fill RBCs.

Evaluation of pretreatments on intra-radicular dentin bond strength of self-adhesive resin cements.

OBJECTIVES: To evaluate the influence of dentin pretreatments on the push-out bond strength (POBS) of self-adhesive resin cements (SARCs) to radicular dentin. MATERIALS AND METHODS: Two experimental pretreatments (2.5% titanium tetrafluoride (TiF4 ) and 26% polyacrylic acid (PA)) and two SARCs: Maxcem Elite (MAX) and Calibra Universal (CAL) were used. For each cement, a control group was applied as indicated by the manufacturer. Sixty bovine incisors were restored (n = 10) and subjected to POBS evaluation. Failure mode, adhesive interface and surface morphology were analyzed by a Scanning Electron Microscopy (SEM) and resin infiltration was performed by confocal laser scanning microscopy (CLSM). Data for POBS and CLSM were analyzed by three-way ANOVA and Bonferroni post-hoc (α = 0.05). RESULTS: For MAX, both experimental pretreatments resulted in increased POBS in the cervical third, and for CAL, only the PA resulted in higher POBS in the cervical third. The most failures occurred between the dentin and the resin cement, except when TiF4 was applied. For PA, analysis of surface morphology showed open dentinal tubules, while TiF4 presented particle agglomerates. SEM and CLSM images confirmed presence of resin tags for both pretreatments. CONCLUSION: Pretreating radicular dentin with PA and TiF4 solutions improves the bond strength of SARCs.

Proliferative diabetic retinopathy treated with intravitreal ranibizumab and photocoagulation directed at ischemic retinal areas-A randomized study.

PURPOSE: To compare ETDRS panretinal laser photocoagulation (PRP) combined with intravitreal injection of ranibizumab (IVR) and photocoagulation targeted to ischemic retina (PIR) combined with IVR in patients with proliferative diabetic retinopathy (PDR). METHODS: PDR patients were randomly assigned to treatment with either PRP + IVR or PIR + IVR. ETRDS Best-corrected visual acuity (BCVA) and central subfield thickness (CSFT) measured on optic-coherence tomography images (OCT-Heidelberg Spectralis) were recorded at baseline and every 4 weeks for one year. Fluorescein leakage area (FLA) from active new vessels was measured every 12 weeks. Full-field ERG was recorded by means of DTL electrodes, following ISCEV standard recommendations, at baseline and after 3 months. RESULTS: Twenty-eight eyes completed the study period. At baseline, mean ± SE BCVA (logMAR) was 0.44 ± 0.07 and 0.37 ± 0.08 (P = 0.5030); CSFT (µm) was 324.0 ± 20.4 and 330.1 ± 22.1 (P = 0.8417); and FLA (mm2) was 16.10 ± 4.42 and 9.97 ± 1.83 (P = 0.2114) for PRP + IVR and PIR + IVR groups, respectively. There were no relevant changes on BCVA or CSFT, but a significant reduction for FLA was observed at all visits compared to baseline for both groups, with no differences between groups. ERG showed at baseline reduced dark-adapted amplitudes, and these changes were also significantly amplified after laser treatment. ROD b-wave amplitude was further reduced in 62 ± 6% for PRP + IVR and 59 ± 4% for group PIR + IVR, but with no between-groups significant difference (P = 0.9082). CONCLUSIONS: PIR + IVR or PRP + IVR are comparable strategies regarding FLA control in PDR and led to similar retinal function impairment, based on ERG changes up to one-year follow-up. TRIAL REGISTRATION NUMBER: NCT03904056, date of registration 02/11/2019, retrospectively registered.

Assessment of the safety of intravitreal injection of metoprolol tartrate in rabbits.

PURPOSE: To verify the safety of different doses of intravitreal metoprolol tartrate (MT) after intravitreal injection in rabbit eyes. METHODS: Animals were randomly assigned into 2 groups: group I received 50 µg of MT and group II 100 µg of MT. A volume of 0.05 mL of the drug solution was administered through an intravitreal injection, while the control eyes received an equal volume of saline solution. Safety was assessed by clinical observation, electroretinography (ERG) and histological evaluation. RESULTS: No evidence of clinical toxicity was observed. ERG waveforms from the MT treated eyes were similar to those recorded from the control eyes in dark-adapted state, amplitude and the implicit time are similar between the groups in light-adapted state, and their retinas had no signs of toxicity by histological evaluation 7 days after intravitreal injection. CONCLUSIONS: The intravitreal use of metoprolol at 50 and 100 µg dosages does not cause short-term retinal toxicity in rabbits.

Intravitreal metoprolol for circumscribed choroidal hemangiomas: a phase I clinical trial.

BACKGROUND: Choroidal hemangioma is a visual threatening condition for which treatments is neither uniform nor widely available. New management options are necessary. The purpose of this study is to assess the safety and early outcome of intravitreal metoprolol tartrate in five patients with CCH. METHODS: Five eyes of five patients diagnosed with subfoveal or peripapillary CCH and unsuccessfully treated with intravitreal anti-VEGF agents were enrolled and received off-label intravitreal injections of metoprolol (50µg/0.05 ml). Baseline and follow-up evaluations included best-corrected visual acuity, intraocular pressure measurement, assessment of anterior chamber cellular score/flare and vitritis, retinography, fundus autofluorescence, and ERG. Patients were followed for a period of 30 days. Statistical analysis involved comparison of pre- and post-treatment findings using a paired t-test. RESULTS: There was no significant difference in all ERG parameters regarding a- and b-wave amplitude and implicit time, and oscillatory potentials' maximal amplitude. There were no significant changes in visual acuity. None of the patients developed clinical signs of intraocular inflammation. The subretinal and/or intraretinal fluid improved in 3 out of 5 patients 4 weeks after the metoprolol injection. CONCLUSIONS: Patients with CCH treated with a single injection of 50µg/0.05ml intravitreal metoprolol injections showed no signs of acute ocular toxicity. This pilot study did not assess long-term retinal toxicity, different concentrations, drug resistance, and complications from repeated-intravitreal injections.

Combined pars plana vitrectomy (PPV) and phacoemulsification (phaco) versus PPV and deferred phaco for phakic patients with full-thickness macular hole (FTMH) and no significant cataract at baseline: 1-year outcomes of a randomized trial combined PPV/phaco vs PPV/deferred phaco for MH.

PURPOSE: To compare functional and anatomic outcomes of combined pars plana vitrectomy (PPV) and phacoemulsification (phaco) versus PPV and deferred phaco in patients with full-thickness macular hole (FTMH) and no significant cataract. METHODS: Thirty-four patients were randomized to group 1 (combined PPV/phaco) and 34 to group 2 (PPV/deferred phaco). Group 2 patients could undergo phaco any time after FTMH surgery if significant cataract developed. RESULTS: Sixty-five patients (33 group 1 and 32 group 2) completed the 12-month visit. Mean ± SEM logMAR best-corrected visual acuity (BCVA) was 0.92 ± 0.04 and 0.90 ± 0.04 at baseline and improved significantly to 0.60 ± 0.05 and 0.58 ± 0.05 at month 12 (p < 0.0001) in groups 1 and 2, respectively. There was no significant difference between the groups in mean BCVA at baseline or at month 12. Mean macular sensitivity (dB) was 18.22 ± 0.93 and 16.72 ± 0.93 at baseline and increased to 21.13 ± 0.86 and 21.07 ± 0.85 in groups 1 and 2, respectively (p < 0.05) with no significant difference between the groups (p = 0.449) at month 12. FTMH closure rate was 73% and 75% in groups 1 and 2, respectively (p = 0.834). CONCLUSION: Among patients with FTMH and no significant cataract at baseline, combined PPV/phaco was associated with similar BCVA, microperimetry, and FTMH closure outcomes at 1-year compared with PPV/deferred phaco. TRIAL REGISTRATION: ( clinicaltrials.gov.br ): Ensaios clínicos brasileiros: RBR-3wmd9s; UTN number: U1111-1190-5013; Plataforma Brasil CAAE number: 50455415.3.0000.5440; IRB number: 1.433.000.

Flexural strength and microhardness of bulk-fill restorative materials.

BACKGROUND: Bulk-fill materials can facilitate the restorative procedure mainly for deep and wide posterior cavities. The purpose of this study was to evaluate flexural strength (biaxial flexural strength [BFS]) and microhardness (Knoop microhardness [KHN]) at different depths of bulk-fill materials. METHODS: Five bulk-fill materials were tested: two light-curable composite resins, one dual-cure composite, one bioactive restorative, and a high-viscosity glass ionomer. A conventional composite was used as control. BFS and KHN were tested at different depths. Data was analyzed by two- and one-way ANOVAs, respectively and Tukey's post-hoc (α=0.05). RESULTS: The high-viscosity glass ionomer material presented the lowest BFS at all depths. KHN for the two light-curable and the dual-cure bulk-fill resin composites was reduced following an increase in restoration depth, while the conventional composite, the bioactive material, and the high-viscosity glass ionomer were not affected. CONCLUSION: There are differences in the properties of the tested materials at 4 mm depth, showing that the studied properties of some materials vary according to the cavity depth, although the results are material dependent. CLINICAL SIGNIFICANCE: Mechanical properties of light-cured, bulk-fill materials may be affected by inadequate polymerization. Clinicians should consider complementary strategies to achieve adequate polymerization at high-increment depths.

Central mfERG amplitude ratio as a predictor for visual outcome of macular hole surgery.

PURPOSE: To investigate whether visual acuity improvement achieved after surgical treatment for macular hole (MH) can be predicted by preoperative multifocal ERG (mfERG) central/peripheral amplitude ratio. METHODS: Thirty patients with unilateral MH were included. Evaluations with comprehensive ophthalmological examination including best-corrected visual acuity (BCVA) were performed at baseline and 1, 3, 8, 24 and 48 weeks after surgery, while mfERG (Diagnosys LLC; 61 hexagons-30°) and spectral-domain optic coherence tomography (sOCT-Heidelberg Engineering) were performed at baseline and 2 months after surgery. mfERG results are shown by means of the ratio between the amplitudes' average from rings 1 and 2 (central) and rings 4 and 5 (peripheral): the P1 ratio. mfERG data from 20 normally sighted age-matched subjects was used for comparison. A macular hole index (MH index) was defined as the quotient between hole height and base measured on OCT. RESULTS: Twenty-six patients finished the 48-week follow-up. Mean ± SE (logMAR) preoperative BCVA was 0.93 ± 0.22 and improved in 0.25 ± 0.07 at 48 weeks. mfERG P1 ratio was reduced at baseline and increased significantly after surgery. A significant correlation was observed between preoperative P1 ratio and BCVA gain at week 8 (r = -0.42; P = 0.033). There was no significant correlation between preoperative MH index and postoperative BCVA (P > 0.05). CONCLUSION: Retinal function assessed using the ratio between central and peripheral mfERG responses might be used as predictor of visual acuity outcome after macular surgery for MH.

Bevacizumab versus triamcinolone for persistent diabetic macular edema: a randomized clinical trial.

PURPOSE: To evaluate 24-week visual acuity and anatomic outcomes of two "pro re nata" (prn) treatment strategies (intravitreal bevacizumab [IVB] prn versus intravitreal triamcinolone acetonide [IVT] prn) in patients with persistent diabetic macular edema (pDME) after 24 weeks of prn-IVB. METHODS: One hundred eyes with center-involving DME were enrolled and treated with prn-IVB for 24 weeks; at week 24, eyes with pDME (central subfield thickness [CST] on spectral domain optical coherence tomography > 300 µm) were randomized to IVB monthly prn (group I; prn-IVB) or IVT every 3 months prn (group II; prn-IVT) and eyes in which the CST was ≤ 300 µm were assigned to continue prn-IVB (group III). RESULTS: Seventy-four eyes completed a 48-week study period. At week 24, 65 (79.3%) eyes still had DME with CST > 300 µm and, therefore, were randomized to prn-IVB (group I, n = 33) or prn-IVT (group II, n = 32); the remaining 17 (20.7%) eyes had CST ≤ 300 µm and were assigned to continued treatment with prn-IVB (group III). At baseline, mean CST (µm) ± standard error of the mean (SEM) was 447.2 ± 24.4, 478.0 ± 19.7, and 386.0 ± 21.0 in groups I, II, and III, respectively (p > 0.05). At week 48, there was no significant difference in mean CST between groups I and II (369.9 ± 23.3 and 426.0 ± 26.1, respectively; p = 0.9995). A significant reduction in mean CST, compared with baseline, was noted at weeks 28 (p = 0.0002) and 44 (p = 0.0002) in group II. Group I did not show a significant reduction in mean CST compared with baseline at any study visit. There were no significant differences in mean CST between groups I and II at any study visit. At baseline, mean ± SEM best-corrected visual acuity (BCVA) (logMAR) was 0.50 ± 0.00, 0.60 ± 0.10, and 0.50 ± 0.10 in groups I, II, and III, respectively (p > 0.05). At week 48, there was no statistically significant difference in mean BCVA between groups I and II (0.50 ± 0.10 and 0.80 ± 0.10, respectively; p = 0.4473). There was no significant improvement in mean BCVA, as compared with baseline, at any study follow-up visit in any of the groups. Group II demonstrated significantly lower BCVA after 24 weeks of IVT (at week 48) compared with baseline (p = 0.0435). There was no significant difference in mean BCVA between groups I and II at any time-point. CONCLUSION: In eyes with pDME after 24 weeks of treatment with prn-IVB, there was no difference between continued treatment with prn-IVB versus a treatment switch to prn-IVT with respect to mean BCVA or mean CST at week 48. However, BCVA was stable in the prn-IVB group, while prn-IVT was associated with BCVA reduction from baseline and a higher risk of IOP elevation.

Retinal function in eyes with proliferative diabetic retinopathy treated with intravitreal ranibizumab and multispot laser panretinal photocoagulation.

PURPOSE: To compare retinal function changes in eyes with proliferative diabetic retinopathy (PDR) after intravitreal ranibizumab (IVR), combined or not with conventional (ETDRS) or multispot laser panretinal (PASCAL) photocoagulation (PRP). METHODS: This study included laser-naive PDR patients that required PRP. Eyes were randomly and prospectively assigned to receive IVR or IVR combined with PASCAL or EDTRS. PRP was performed at baseline in 1 (PASCAL) or 2 (ETDRS) sessions. In eyes with macular edema, macular short pulse grid laser was associated with IVR at baseline and IVR was repeated monthly or quarterly if neovascularization was detected on angiography. Comprehensive ophthalmological evaluations, including SD-OCT, were performed at baseline and every 4 weeks after treatment. Full-field electroretinography (ERG: extended ISCEV standard) was performed at baseline and at 12, 24 and 48 weeks. RESULTS: IVR = 13, PASCAL = 15 and ETDRS = 15 eyes finished 48-week follow-up. There was a statistically significant BCVA improvement of 0.1-0.3 logMAR in all groups, and fluorescein angiography leakage area (FLA) reduced in 56%, 73%, and 73% from baseline for ETDRS, IVR and PASCAL, respectively, up to 48 weeks without significant differences between groups (p > 0.05). A significant a- and b-wave amplitudes reduction was observed for dark- and light-adapted ERG for ETDRS and PASCAL, but only minor dark-adapted b-wave reduction was found for IVR, up to 48 weeks. As an example, at week 48, combined response b-wave amplitude reduced in 181.5 ± 31.4 µV, 128.0 ± 27.9 µV and 82.4 ± 15.2 µV for ETDRS, PASCAL and IVR (p < 0.05 each group), respectively. No significant difference was observed between ETDRS and PASCAL for any ERG parameter. CONCLUSIONS: IVR combined with single or multiple spot PRP causes similar retinal function impairment during 48 weeks of observation, while IVR alone seems to be similarly effective controlling FLA without changing retinal function.

Enhancement of astaxanthin production from Haematococcus pluvialis under autotrophic growth conditions by a sequential stress strategy.

The study of microalgal culture has been growing in recent decades, because the cellular structure of microalgae has diverse highly valuable metabolites that have attract attention of numerous companies and research groups. The pigment astaxanthin is considered one of the most powerful antioxidants in nature. The microalga Haematococcus pluvialis was proposed as one of the best natural astaxanthin sources, because it can accumulate high amount of the pigment. In this work, we studied different stress treatments on H. pluvialis growth cultures as well as astaxanthin production under autotrophic growth conditions. The results showed that extending nitrogen starvation before increasing radiation intensity up to 110 µmol photons m-2 s-1 during late the palmella cell phase incremented the astaxanthin concentration up to 2.7% of dry biomass with an efficient light energy utilization during the stress stage.

In vivo release and retinal toxicity of cyclosporine-loaded intravitreal device.

PURPOSE: To determine the in vivo release profile and retinal safety of cyclosporine A (CsA) delivered from a biodegradable poly-lactide-co-glycolide (PLGA) device in the vitreous cavity of rabbits' eyes. METHODS: A total of 60 animals (60 eyes) divided into two groups were used. For the in vivo release study, 32 eyes received PLGA implants containing 350 µg of CsA, and 16 eyes received the implants without drug (control). Four animals of CsA group and two of the control group were killed weekly until 8 weeks; the vitreous was removed, and CsA concentration was evaluated. Ophthalmological examination was performed in the animals prior to implant placement and weekly during the study period. Electroretinography (ERG) was performed in other six animals for each group, treated and control, at the beginning and at the end of the study (8 weeks) when they were killed and had their eyes processed for histology. RESULTS: No sign of inflammation was noticed on slit lamp examinations and the IOP maintained stable during the study period in CsA and control groups. CsA concentration in the vitreous (ng/ml) was 257.07 ± 117.23, 271.15 ± 98.96, 296.66 ± 86.25, 256.27 ± 99.22, 304.50 ± 88.18, 326.35 ± 105.24, 491.25 ± 119.90 and 589.93 ± 132.55 after 1, 2, 3, 4, 5, 6, 7 and 8 weeks of implantation, respectively. At the end of the study, 21.67 % of mass loss was found. The retina did not show any histological alteration in either group, but a significant reduction in dark-adapted b-wave amplitude was observed in the CsA group, with no changes in a-wave amplitude. CONCLUSIONS: These data show that the PLGA system is safe, but the selective reduction in ERG b-wave amplitude indicates that the PLGA with 350 µg CsA causes retinal function impairment, specifically on the rod postreceptor pathway, 8 weeks after implantation. These ERG changes were not associated with any histological damage as seen at the light microscopy level.

Neuroprotective effects of intravitreal triamcinolone acetonide and dexamethasone implant in rabbit retinas after pars plana vitrectomy and silicone oil injection.

PURPOSE: To investigate potential retinal neuroprotective effects of intravitreal triamcinolone acetonide and dexamethasone implant in rabbits after pars plana vitrectomy and intravitreal silicone oil injection. METHODS: The right eyes of 84 rabbits, divided into 3 groups of 28 rabbits each, underwent standard 3-port pars plana vitrectomy with silicone oil (SO group), silicone oil and intravitreal dexamethasone implant (SO/DEX group), or silicone oil and triamcinolone acetonide (SO/TA group). The retina from the left eye of each rabbit served as a control. The animals were killed at 4 weeks after surgery. Qualitative and quantitative histopathologic analyses were performed 4 weeks after surgery, and investigation for apoptosis was performed using the Tunel assay. RESULTS: Intravitreal triamcinolone acetonide and dexamethasone implant were associated with increased retinal neuronal survival, primarily in the outer nuclear layer, inner nuclear layer, and ganglion cell layer. In the SO group, the cell density in eyes that underwent PPV/SO was 31% lower in the outer nuclear layer, 33% lower in the inner nuclear layer, and 45% lower in the ganglion cell layer compared to control eyes (p < 0.05 for all PPV/SO versus control comparisons). Compared to eyes that underwent PPV/SO, the cell density in eyes treated with triamcinolone was 27% higher in the outer nuclear layer, 66% higher in the inner nuclear layer, and 100% higher in the ganglion cell layer (p < 0.05 for all triamcinolone versus PPV/SO comparisons). Compared to eyes that underwent PPV/SO, the cell density in eyes treated with dexamethasone was 46% higher in the outer nuclear layer, 62% higher in the inner nuclear layer, and 77% higher in the ganglion cell layer (p < 0.05 for all dexamethasone versus PPV/SO comparisons). Analyses using the Tunnel assay demonstrated apoptotic bodies in all eyes in the SO group, compared with none of the eyes in the SO/TA and SO/DEX groups. The presence of cell nuclei stained with 49,6-diamidino-2-phenylindole (DAPI) was demonstrated in all groups. CONCLUSION: In this experimental model of neuroprotection, increased retinal neuronal survival was seen in the steroid-treated groups compared with the controls.

Applications of ChatGPT in the diagnosis, management, education, and research of retinal diseases: a scoping review.

PURPOSE: This scoping review aims to explore the current applications of ChatGPT in the retina field, highlighting its potential, challenges, and limitations. METHODS: A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, MEDLINE, and Embase, to identify relevant articles published from 2022 onwards. The inclusion criteria focused on studies evaluating the use of ChatGPT in retinal healthcare. Data were extracted and synthesized to map the scope of ChatGPT's applications in retinal care, categorizing articles into various practical application areas such as academic research, charting, coding, diagnosis, disease management, and patient counseling. RESULTS: A total of 68 articles were included in the review, distributed across several categories: 8 related to academics and research, 5 to charting, 1 to coding and billing, 44 to diagnosis, 49 to disease management, 2 to literature consulting, 23 to medical education, and 33 to patient counseling. Many articles were classified into multiple categories due to overlapping topics. The findings indicate that while ChatGPT shows significant promise in areas such as medical education and diagnostic support, concerns regarding accuracy, reliability, and the potential for misinformation remain prevalent. CONCLUSION: ChatGPT offers substantial potential in advancing retinal healthcare by supporting clinical decision-making, enhancing patient education, and automating administrative tasks. However, its current limitations, particularly in clinical accuracy and the risk of generating misinformation, necessitate cautious integration into practice, with continuous oversight from healthcare professionals. Future developments should focus on improving accuracy, incorporating up-to-date medical guidelines, and minimizing the risks associated with AI-driven healthcare tools.

Endogenous endophthalmitis due to Escherichia coli: a case report.

Endophthalmitis is a severe form of purulent inflammation caused by the infection of the intraocular tissues or fluids. This infection infrequently occurs through endogenous routes, which are often correlated with major risk factors. Escherichia coli, a gram-negative rod, can cause endophthalmitis through hematogenous spread. We here report a 59-year-old man who presented to our service with acute visual impairment in his left eye, preceded by floaters. He was taking sirolimus and azathioprine for a transplanted kidney, had undergone catheterization for bladder atresia, and had a history of recurrent E. coli urinary tract infections. On evaluation, the left eye exhibited visual acuity of hand motion, anterior chamber reaction (3+/4+), and intense vitritis (4+/4+) with white flake clusters, which prevented appropriate retinal evaluation. Pars plana vitrectomy was performed, and the culture yielded E. coli. The present case highlights the importance of identifying the signs and symptoms of infection early so that diagnosis and treatment of endophthalmitis can be promptly initiated.

Short pulse grid and subthreshold micropulse laser (the sandwich grid) plus intravitreal ranibizumab for the treatment of diabetic macular edema.

OBJECTIVE: To investigate the effects of two laser treatment procedures combined, short pulse grid laser (SP) and subthreshold micropulse laser (MP) (the sandwich grid [SWG] technique), plus intravitreal ranibizumab (IVR) on central subfield thickness (CSFT), best-corrected visual acuity (BCVA) and macular sensitivity in patients with diabetic macular edema (DME). METHODS: Forty-five eyes (of 33 patients) with center-involving DME were treated with the SWG laser technique plus IVR and followed for 12 months. Laser treatment was performed at baseline: SP laser spots were placed in a grid pattern in the macular area (500 µm from the fovea) according to the extension of DME; subsequently, MP laser was delivered up to the edge of the fovea. MP laser re-treatment sessions could be performed every 3 months if DME was present and CSFT was ≥ 300 µm on SD-OCT. IVR injection was performed at baseline and repeated monthly if CSFT > 300µm. Preoperatively and monthly, ophthalmological examination was performed including measurements of BCVA, CSFT, and macular sensitivity. RESULTS: One-year follow-up data is available for 37 eyes of 27 patients. Mean ± SE CSFT (µm) was 509.36 ± 25.14 and 325.76 ± 15.34 at baseline and 12 months, respectively. A significant reduction in mean CSFT was observed at all study visits compared to baseline (p < 0.001). Mean ± SE BCVA (logMAR) was 0.62 ± 0.04 and 0.45 ± 0.04 at baseline and 12 months, respectively. A significant improvement in mean BCVA was observed at all study visits compared to baseline (p < 0.001). Mean ± SE macular sensitivity (dB) was 17.85 ± 0.80 and improved to 19.05 ± 0.59 after one year of follow-up (p = 0.006). The mean number of IVR injections was 8.29 ± 0.63. The mean number of MP laser procedures including the initial SWG laser session was 3.67 ± 0.22. No ocular or systemic adverse effects were observed. CONCLUSION: The SWG laser technique plus IVR was associated with significant improvement in macular edema, BCVA, and macular sensitivity in patients with center-involving DME. CLINICAL TRIAL NUMBER (CAAE): 22969019.4.0000.5440.