Morphologic Features of Regulated vs. Dysregulated Rhegmatogenous Retinal Detachment Using Swept-Source Optical Coherence Tomography.

OBJECTIVE: To describe varying morphological features of patients with RRD based on the extent of regulation of the subretinal space by the retinal pigment epithelium (RPE) pump using swept-source optical coherence tomography (SS-OCT). DESIGN: Prospective clinical cohort study. Methods SETTING: St. Michael's Hospital, Toronto, Canada, from August 2020-August 2023. PARTICIPANTS: 120 consecutive eyes with primary RRD. COHORTS: Subclinical, non-progressive, localized RRD defined as regulated vs. acute, progressive, and extensive defined as dysregulated assessed with swept-source SS-OCT. MAIN OUTCOME: Morphological features of regulated vs dysregulated RRDs with SS-OCT. RESULTS: 19.2 % (23/120) of RRDs were classified as regulated and 80.8% (97/120) were dysregulated. The mean age of patients with regulated RRDs was 37.1 years (±13.7 SD) versus 62.6 years (±11.6SD) for patients with dysregulated RRDs (P<0.001). The presence of outer retinal corrugations (ORCs) on OCT was observed in 4.3%(1/23) of regulated vs 81.4% (79/97) of dysregulated RRDs (P<0.001). CME was found in 41.6%(5/12) of regulated RRDs compared to 87.3%(83/95) of dysregulated RRDs(P<0.001). ORC presence was an independent predictor of having a dysregulated RRD (P= 0.02,ß = 6.6,95 %CI [1.3 -33.2]) when controlling for age, sex, baseline VA, lens status, and RD extent. Among patients with regulated RRDs, 25.0% (3/12) were in Stage 2, 0% (0/16) in Stage 3A, 8.3% (1/12) in Stage 3B, 0% (0/16) in Stage 4, and 66.7% (8/12) in Stage 5. In patients with dysregulated RRDs, 14.7% (14/95) were in Stage 2, 15.7% (15/95) were in Stage 3A, 37.9% (36/95) in Stage 3B, 22.1% (21/95) in Stage 4, and 9.5% (9/95) in Stage 5 (P<0.001). CONCLUSIONS: There are significant morphologic differences between regulated and dysregulated RRDs using SS-OCT. ORCs are present in almost all dysregulated cases but in a minority of regulated cases and they are an independent predictor of RPE-photoreceptor regulation status. Demographic and clinical features differentiate regulated and dysregulated RRD and understanding these differences has significant implications for optimal management and postoperative outcomes.

VALIDATION OF M-CHARTS FOR QUANTITATIVE ASSESSMENT OF METAMORPHOPSIA FOLLOWING RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To validate the quantitative assessment of metamorphopsia in rhegmatogenous retinal detachment (RRD) using M-CHARTS by determining its correlation with subjective reporting of metamorphopsia with a validated metamorphopsia questionnaire (modified MeMoQ). METHODS: The Research Ethics Board approved a prospective observational study carried out at St. Michael's Hospital, Toronto, Canada. Patients with primary, unilateral RRD and healthy controls were included. Metamorphopsia at 3 months was assessed with modified MeMoQ and M-CHARTS. RESULTS: One hundred patients (50 with RRD, 50 controls) were included. Seventy percent (35/50) of the RRD group had metamorphopsia with M-CHARTS and 80% (40/50) with MeMoQ. The modified MeMoQ and total M-CHARTS scores were significantly higher in patients with RRD compared with controls ( P < 0.0001). Cronbach's alpha reliability coefficient was 0.934 in the RRD group. Horizontal, vertical, and total M-CHARTS scores were significantly correlated with MeMoQ scores (r s  = 0.465, P = 0.0007; r s  = 0.405, P = 0.004; r s  = 0.475, P = 0.0005, respectively). M-CHARTS was 72.7% sensitive and 94.6% specific for detection of metamorphopsia (positive score ≥ 0.2), with an area under the receiver operating characteristic curve = 0.801. A stronger correlation was found in patients who scored ≥0.2 on the M-CHARTS and reported metamorphopsia with the MeMoQ (r s  = 0.454, P = 0.001). CONCLUSION: The authors have validated M-CHARTS as a tool to quantitatively assess metamorphopsia in patients with RRD, which is significantly correlated with patient-reported outcomes using the MeMoQ. A total score of ≥0.2 with M-CHARTS was more strongly correlated with MeMoQ.

ASSOCIATION OF INTRAVENOUS FLUORESCEIN ANGIOGRAPHY AND ADAPTIVE OPTICS IMAGING IN DIABETIC RETINOPATHY: A Prospective Case Series.

PURPOSE: To our knowledge, we present the first case series investigating the relationship between adaptive optics (AO) imaging and intravenous fluorescein angiography (IVFA) parameters in patients with diabetic retinopathy. METHODS: Consecutive patients with diabetic retinopathy older than age 18 years presenting to a single center in Toronto, Canada, from 2020 to 2021 were recruited. Adaptive optics was performed with the RTX1 camera (Imagine Eyes, Orsay, France) at retinal eccentricities of 2° and 4°. Intravenous fluorescein angiography was assessed with the artificial intelligence-based RETICAD system to extract blood flow, perfusion, and blood-retinal-barrier (BRB) permeability at the same retinal locations. Correlations between AO and IVFA parameters were calculated using Pearson's correlation coefficient. RESULTS: Across nine cases, a significant positive correlation existed between photoreceptor spacing on AO and BRB permeability (r = 0.303, P = 0.027), as well as perfusion (r = 0.272, P = 0.049) on IVFA. When stratified by location, a significant positive correlation between photoreceptor dispersion and both BRB permeability and perfusion (r = 0.770, P = 0.043; r = 0.846, P = 0.034, respectively) was observed. Cone density was also negatively correlated with BRB permeability (r = -0.819, P = 0.046). CONCLUSION: Photoreceptor spacing on AO was significantly correlated with BRB permeability and perfusion on IVFA in patients with diabetic retinopathy. Future studies with larger sample sizes are needed to understand the relationship between AO and IVFA parameters in diverse patient populations.

Histological changes in retinal detachment: A systematic review for the clinician.

Although there have been numerous innovations in the management of retinal detachment (RD) over the past decades, there is still limited understanding of the pathophysiological processes that take place before and after repair. Summarizing key concepts using animal studies may allow for a better assessment of common pre- and postoperative microstructural abnormalities in RD. We performed a systematic literature review on Ovid MEDLINE, EMBASE, and Cochrane Controlled Register of Trials from January 1968 to January 2022, searching animal or human studies reporting retinal histologic changes following primary or induced RD. Thirty-two studies were included. Main cellular events were summarized: photoceptor apoptosis occurs as early as 12 hours after RD and, although most cells survive, there is extensive remodeling. Outer segments progressively degenerate, while inner segments are reorganized. Rod and cone opsins are redistributed, and rod axons retract while cones undergo changes in shape. Second- and third-order neurons rearrange their dendritic processes, and Müller cells become hypertrophic, growing into the subretinal space. Finally, retinal pigment epithelium cells undergo a change in their morphology. Acknowledging critical morphologic changes following RD is crucial in understanding why anatomical and functional outcomes can vary. Insights from histological studies, together with high-resolution imaging, may be key in identifying novel biomarkers in RD.

In-Office Suprachoroidal Viscopexy for Rhegmatogenous Retinal Detachment Repair.

Importance: In-office suprachoroidal viscopexy (SCVEXY) is a minimally invasive technique for rhegmatogenous retinal detachment (RRD) repair that can be performed with no incision, no tamponade agent, and no positioning requirements. This technique has the potential to be a step forward in the armamentarium to treat RRDs. Objective: To describe in-office SCVEXY for RRD repair. Design, Setting, and Participant: In this single-case report with short follow-up, a man in his 50s with pseudophakia and recent visual loss presented to St Michael's Hospital, Unity Health Toronto, with a fovea-off RRD in the right eye, extending from 6 to 10 o'clock, with no visible causative retinal break. Exposure: Injection of suprachoroidal sodium hyaluronate, 1%, in the region of the suspected break, using a 30-gauge needle with a custom-made guard that exposed only 1 mm of the needle. Main Outcome and Measures: Ability to perform in-office SCVEXY and to obtain a visible choroidal indentation. Results: After the procedure, a dome-shaped choroidal convexity was present in the superior temporal area. The patient achieved macular reattachment in less than 24 hours with no postoperative abnormalities, such as outer retinal folds, residual subfoveal fluid, or retinal displacement, with rapid recovery of the outer retinal bands on optical coherence tomography. The optical coherence tomography scans acquired in the area of the choroidal convexity demonstrated the location of the viscoelastic material in the suprachoroidal space. Laser retinopexy was applied in the suspected region of the retinal tear, and the patient was able to resume normal activity immediately after the procedure with no restrictions. Conclusions and Relevance: Suprachoroidal viscopexy is feasible as an in-office technique to create a temporary choroidal buckle for RRD repair. It is a minimally invasive procedure with the potential to maximize anatomical outcomes of integrity and postoperative functional outcomes in RRD because its mechanism of action does not require drainage of subretinal fluid or intraocular gas tamponade. Nevertheless, this was a single-case report with short follow-up, which limits the ability to determine the procedure's benefits, potential adverse events, failure rates, and best-case selection. Further work is required to refine the procedure and assess its efficacy and safety.

Pneumatic Retinopexy for Rhegmatogenous Retinal Detachment in Elderly Patients.

PURPOSE: To assess clinical outcomes in elderly patients aged ≥ 75 years who underwent pneumatic retinopexy (PnR) for primary rhegmatogenous retinal detachment (RRD). DESIGN: Retrospective cohort study. SUBJECTS: Patients aged ≥ 75 years with primary RRD undergoing PnR. METHODS: This study evaluates clinical outcomes among eligible patients who presented from October 1, 2010, to December 31, 2022, with a minimum of 3 months' follow-up. There were no limitations with respect to the number, size, or location of retinal breaks. Exclusion criteria included significant proliferative vitreoretinopathy or previous retinal detachment repair in the index eye, inability to maintain the postoperative posturing requirements or inability to carry out adequate examination of the peripheral retina because of media opacity. Lens status did not impact the decision to offer PnR. MAIN OUTCOME MEASURES: Pneumatic retinopexy primary anatomic reattachment rate and postoperative best corrected visual acuity (BCVA) at 3 months. RESULTS: Eighty patients with a mean age of 80.6 ± 4.6 years were included in this study; 35% (28/80) were phakic and 34% (27/80) presented with a fovea-on RRD. The mean number of breaks in the detached retina was 1.52 ± 1.13, and the mean number of quadrants of detached retina was 2.35 ± 0.93. The primary anatomic reattachment rate at 3 months after PnR was 78.8% (63/80), whereas the remaining 21.2% (17/80) failed PnR and underwent an operating room procedure. There was a statistically significant improvement in logarithm of the minimum angle of resolution (logMAR) BCVA from baseline to 3 months (1.29 ± 0.94 and 0.69 ± 0.67, respectively, P < 0.001). A subgroup analysis that only included patients aged > 80 years was also performed, with a total of 39 patients with a mean age of 84.4 ± 3.5 years. The primary anatomic reattachment rate with PnR in this subgroup was 74.4% (29/39), with a statistically significant improvement in BCVA from baseline to 3 months (1.4 ± 1.05 and 0.77 ± 0.70, respectively; P = 0.004). CONCLUSIONS: Elderly patients treated with PnR for primary RRD had relatively comparable primary anatomic reattachment rates with other surgical techniques such as pars plana vitrectomy and scleral buckle. Pneumatic retinopexy is an effective, minimally invasive office-based procedure that may be desirable for some elderly patients. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.

Pathophysiology of outer retinal corrugations: Imaging dataset and mechanical models.

This article presents high-resolution swept-source optical coherence tomography (SS-OCT) imaging data used to elaborate a mechanical model that elucidates the formation of outer retinal corrugations (ORCs) in rhegmatogenous retinal detachments (RRD). The imaging data shared in the repository and presented in this article is related to the research paper entitled "Outer Retinal Corrugations in Rhegmatogenous Retinal Detachment: The Retinal Pigment Epithelium-Photoreceptor Dysregulation Theory" (Muni et al., AJO, 2022). The dataset consists of 69 baseline cross-sectional SS-OCT scans from 66 patients that were assessed for the presence of ORCs and analyzed considering the clinical features of each case. From the 66 cases, we selected SS-OCT images of 4 RRD patients with visible ORCs and no cystoid macular edema (CME) to validate the mechanical model. We modelled the retina as a composite material consisting of the outer retinal layer (photoreceptor layer) and the inner retinal layer (the part of the retina that excludes the photoreceptor layer) with thicknesses T o and T i and elastic modulus E o and E i , respectively. The thickness of the outer and inner retinal layers and the relative increase in the length of the outer retinal layer (γ) were measured from the SS-OCT images. Measurements from the SS-OCT images of patients with RRD demonstrated a 30% increase (γ=0.3) in the length of the outer retinal layer and a 400% increase in the thickness of the outer retinal layer (To). Using the mathematical model, Eo/Ei ranged between 0.05 to 0.5 to result in ORCs with a similar frequency to those observed in the SS-OCT scans.

Outer Retinal Corrugations in Rhegmatogenous Retinal Detachment: The Retinal Pigment Epithelium-Photoreceptor Dysregulation Theory.

PURPOSE: Outer retinal folds occur when outer retinal corrugations (ORCs) persist after retinal reattachment with worse functional outcomes. We investigate the pathophysiology of ORCs in vivo. DESIGN: Prospective cohort study. METHODS: Patients with rhegmatogenous retinal detachment (RRD) presenting to St. Michael's Hospital, Toronto, Ontario, Canada, between August 2020 and February 2022 were assessed with swept-source optical coherence tomography (SS-OCT) and ultra-widefield SS-OCT for ORCs. Clinical characteristics of eyes with/without ORCs were compared. Mathematical models were used to deduce mechanical properties leading to ORCs. RESULTS: Sixty-six patients were included. More than half (60.6%, 40/66) were fovea-off and 48.4% (32/66) had ORCs at presentation. All eyes (32/32) with ORCs had retinal pigment epithelium (RPE)-photoreceptor dysregulation for at least 2 days, defined as loss of RPE control with acute, progressive, and extensive RRDs. In all (34/34) eyes without ORCs the RPE was in relative control of the subretinal space with nonprogressive subclinical or small localized or resolving RRDs, or with RPE-photoreceptor dysregulation for fewer than 2 days. Mathematical models indicate that a modulus of elasticity of the outer retina relative to the inner retina of 0.05 to 0.5 leads to ORCs. CONCLUSIONS: ORCs develop with (1) acute exposure of subretinal space to liquified vitreous, (2) for >2 days, that (3) overwhelms RPE capacity, leading to progressive and extensive RRD. Mathematical models suggest that a reduction in the modulus of elasticity of the outer retina occurs such that intrinsic compressive forces, likely related to progressive outer retinal hydration and lateral expansion, lead to ORCs. Understanding the pathophysiology of ORCs has implications for management.

Avaliação das alterações cardiotóxicas decorrentes do uso da doxorrubicina: estudo experimental em ratos / Clinical evaluation of the doxorubicin-induced cardiotoxicity: experimental study in rats

A doxorrubicina é um dos quimioterápicos mais utilizados no tratamento de tumores sólidos e hematopoiéticos, embora possa causar reações adversas, especialmente cardiomiopatia secundßria. Apesar do potencial cardiotóxico, a doxorrubicina ainda é amplamente utilizada devido a sua alta eficßcia e baixo custo. esse trabalho objetiva-se estudar a sintomatologia associada ao uso da doxorrubicina em ratos, para elucidar seus efeitos cardiotóxicos. Dez ratos Wistar machos foram distribuidos em dois grupos: tratado, o qual recebeu 5mg/kg de doxorrubicina em 1,0mL de salina, via intraperitoneal a cada sete dias, durante quatro se- manas; e controle, o qual recebeu apenas 1,0 mL de salina nas mesmas condições descritas. Realizou-se eletrocardiograma antes dos tratamentos e após quatro semanas, juntamente com ecocardiograma. Os animais do grupo tratado apresentaram apatia, emagrecimento, desidratação e fezes diarreicas com muco, indicando disfunção metabólica decorrente da toxicidade do quimioterßpico. Em dois animais, o quadro clínico evoluiu para óbito, 19 dias após início do tratamento. No eletrocardiograma detectou-se aumento na amplitude das ondas P e R, sugerindo sobrecarga atrial e ventricular esquerda, respectivamente. A onda T apresentou amplitude superior à onda R, provavelmente devido a alterações eletrolíticas secundßrias ao quadro de desidratação e diarreia. Arritmias atriais e ventriculares, contudo, não foram detectadas. Foi diagnosticada disfunção ventricular nos animais que receberam doxorrubicina, quando avaliados por ecocardiografia de deformação miocßrdica (velocidade e deslocamento radiais do ventrículo esquerdo). Conclui-se que a doxorrubicina provoca cardiotoxicidade dose-dependente com redução progressiva da função ventricular esquerda, a qual pode ser diagnosticada precocemente com a ecocardiografia strain...

Doxorubicin is one of lhe most common drugs used in lhe treatment of solid and emopoietic tumors; however it causes a dose-dependet adverse effects, mainly cardiomyopathy. Despite the obvious cardiac toxicity potential, doxorubicin is still widely used due t0 its high efficiency and low cost. Therefore, this research aims to study the sytmptoms associated with the use of doxorubicin in rats, in order to elucidate its cardiac toxicity. Ten male Wistar rats were distributed into two groups: treated, which received 5mg/kg of doxorubicin in 1.0 mL saline intraperitoneal weekly, for four weeks, and control, which received only 1.0 mL of saline under lhe same conditions described. Electrocardiography was performed before treatment and atter four weeks when echocardiography was done as well. The treated group showed apathy, weight loss, dehydration and diarrheal stools with mucus, indicating metabolic dystunction due to the toxicity of chemotherapy. Two animals died, 19 days after lhe beginning of the experiment The electrocardiogram detected an increase in the amplitude of P. R and S waves, suggesting atrial and ventricular overload, respectively. The greater amplitude of the T-wave when compared to the R wave occurred probably due to electrolyte alterations caused by dehydration and diarrhea. Nevertheless, atrial and ventricular ar- rhythmias were not detected. Ventricular dysfunction was diagnosed in animais that received doxorubicin when evaluated by strain echocardiography (left ventricular radial velocity and displacement). It was concluded that doxorubicin causes a dose-dependent cardiotoxicity, with a progressive left ventricular dysfunction which may be early detected using the strain echocardiography...