Settings and Clinical Applications of Subthreshold Micropulse Laser Therapy: A Review.

Subthreshold lasers operate below the threshold of visible tissue damage, thereby preventing ophthalmoscopically visible thermal damage to the chorio-retinal layers. They could represent a safe and effective alternative and/or adjunctive procedure to conventional lasers in treating diabetic macula edema (DME), central serous chorioretinopathy (CSCR), and branch retina vein occlusion (BRVO). This review focuses on the use of subthreshold micropulse laser (SMPL), its settings, and clinical applications. Despite their widespread use, a standardized protocol for sub-threshold laser settings has not been established yet, and thus, there is uncertainty in selecting effective and safe parameters for any specific situation. We conducted a comprehensive overview of the existing indications for subthreshold laser therapy and their settings for different retinal diseases. The debate revolves around which parameters could guarantee the safety of the procedure for each case, depending on the duty cycle, the laser wavelength, the spot duration, and the power, with laser power titration on one side or choosing a fixed lowered power value on the other side. SMPL therapy for DME, CSCR, and BRVO-associated macular edema has shown significant effectiveness in reducing the macular thickness, facilitating subretinal fluid absorptions, increasing the best corrected visual acuity (BCVA) and reducing the number of intravitreal injections (IVI) required annually. We presented a broad list of the laser parameters reported in the literature, organized into different tables divided based on the specific pathology, with the aim of providing a useful tool for future studies.

Small-Incision new generation implantable miniature telescope surgical technique and patient outcomes.

BACKGROUND: Various ocular implants were suggested as a means of enhancing vision in patients with advanced age related macular degeneration. Recently, a new generation of implantable telescopes has been released. The purpose of this study is to report the surgical technique of implantation along with patient outcomes. METHODS: This work focuses on the surgical technique. Crucial surgical steps are carefully reported along with discussion on main drawbacks and limitations. RESULTS: This approach uses a preloaded delivery system with improved features and requires a smaller incision. First patient outcomes are also reported. CONCLUSIONS: Surgical steps to implant this preloaded intraocular telescope are easier than previous versions, however this remains a complex procedure. Initial patient functional outcomes look promising.

The effect of optical degradation from cataract using a new Deep Learning optical coherence tomography segmentation algorithm.

PURPOSE: To assess the validity of the results of a freely available online Deep Learning segmentation tool and its sensitivity to noise introduced by cataract. METHODS: The OCT images were collected with a Spectralis SD-OCT (Heidelberg Engineering, Heidelberg, Germany) as part of normal clinical practice. Data were segmented using a freely available online tool called Relayer ( https://www.relayer.online/ ), based on a cross-platform Deep Learning segmentation architecture specifically adapted for retinal OCT images. The segmentations were read into MATLAB (The MathWorks, Natick, MA, USA) and analyzed. RESULTS: There was an excellent agreement between the ETDRS measurements obtained from the two algorithms. Upon visual inspection, the segmentation based on Deep Learning obtained with Relayer appeared more accurate except in one case of apparent good quality image showing interrupted segmentations in some of the B-scans. CONCLUSION: A freely available online Deep Learning segmentation tool showed good and promising performance in healthy retinas before and after cataract surgery, proving robust to optical degradation of the image from media opacities.

How to Set Up Genetic Counselling for Inherited Macular Dystrophies: Focus on Genetic Characterization.

Inherited macular dystrophies refer to a group of degenerative conditions that predominantly affect the macula in the spectrum of inherited retinal dystrophies. Recent trends indicate a clear need for genetic assessment services in tertiary referral hospitals. However, establishing such a service can be a complex task due to the diverse skills required and multiple professionals involved. This review aims to provide comprehensive guidelines to enhance the genetic characterization of patients and improve counselling efficacy by combining updated literature with our own experiences. Through this review, we hope to contribute to the establishment of state-of-the-art genetic counselling services for inherited macular dystrophies.

Variability of Visual Recovery with Time in Epiretinal Membrane Surgery: A Predictive Analysis Based on Retinal Layer OCT Thickness Changes.

PURPOSE: To correlate postoperative optical coherence tomography (OCT) thickness changes of each retinal layer with different patterns of visual recovery after idiopathic epiretinal membrane (ERM) surgery in a cohort of patients showing no known risk factors for poor visual recovery at preoperative imaging. METHODS: Best corrected visual acuity (BCVA) and OCT images were acquired preoperatively and 1 month, 3 months and 6 months postoperatively. Patients were divided into four groups according to postoperative BCVA improvement: improvement < 15 ETDRS letters (GROUP 1), immediate improvement of BCVA without further improvements at later follow-ups (GROUP 2), immediate improvement of BCVA with further improvements at later follow-ups (GROUP 3) and delayed improvement of BCVA (GROUP 4). RESULTS: Eighty-five patients were included. GROUP1 was the only one characterized by retinal nerve fiber layer (RNFL) thickness increase and ganglion cell layer/central macular thickness (GCL/CMT) ratio decrease at 1 month and outer nuclear layer (ONL) thickness decrease at 3 and 6 months. GROUP 2 was the only one showing a decrease in GCL/inner plexiform layer (GCL/IPL) ratio at 1 month. GROUP 3 and 4 showed higher preoperative RNFL thickness compared to the other, and GROUP 4 manifested a late increase in RNFL thickness at 6 months. CONCLUSIONS: Different patterns of VA recovery are associated with specific layer thickness changes. If further confirmed, this would help detect those cases characterized by poor or delayed visual recovery despite the absence of other known imaging risk factors.

Trans-Scleral Plugs Fixated FIL SSF IOL: A Review of the Literature and Comparison with Other Secondary IOL Implants.

Purpose. To revise the current literature on FIL SSF (Carlevale) intraocular lens, previously known as Carlevale lens, and to compare their outcomes with those from other secondary IOL implants. Methods. We performed a peer review of the literature regarding FIL SSF IOLs until April 2021 and analyzed the results only of articles with a minimum of 25 cases and a follow-up of at least 6 months. The searches yielded 36 citations, 11 of which were abstracts of meeting presentations that were not included in the analysis because of their limited data. The authors reviewed 25 abstracts and selected six articles of possible clinical relevance to review in full text. Of these, four were considered to be sufficiently clinically relevant. Particularly, we extrapolated data regarding the pre- and postoperative best corrected visual acuities (BCVA) and the complications related to the procedure. The complication rates were then compared with those from a recently published Ophthalmic Technology Assessment by the American Academy of Ophthalmology (AAO) on secondary IOL implants. Results. Four studies with a total of 333 cases were included for results analysis. The BCVA improved in all cases after surgery, as expected. Cystoid macular edema (CME) and increased intraocular pressure were the most common complications, with an incidence of up to 7.4% and 16.5%, respectively. Other IOL types from the AAO report included anterior chamber IOLs, iris fixation IOLs, sutured iris fixation IOLs, sutured scleral fixation IOLs, and sutureless scleral fixation IOLs. There was no statistically significant difference in the rates of postoperative CME (p = 0.20), and vitreous hemorrhage (p = 0.89) between other secondary implants and the FIL SSF IOL, whereas the rate of retinal detachment was significantly less with FIL SSF IOLs (p = 0.04). Conclusion. The results of our study suggest the implantation of FIL SSF IOLs is an effective and safe surgical strategy in cases where there is a lack of capsular support. In fact, their outcomes seem to be comparable to those obtained with the other available secondary IOL implants. According to published literature, the FIL SSF (Carlevale) IOL provides favorable functional results with a low rate of postoperative complications.

Genetic Aspects of Age-Related Macular Degeneration and Their Therapeutic Potential.

Age-related macular degeneration (AMD) is a complex and multifactorial disease, resulting from the interaction of environmental and genetic factors. The continuous discovery of associations between genetic polymorphisms and AMD gives reason for the pivotal role attributed to the genetic component to its development. In that light, genetic tests and polygenic scores have been created to predict the risk of development and response to therapy. Still, none of them have yet been validated. Furthermore, there is no evidence from a clinical trial that the determination of the individual genetic structure can improve treatment outcomes. In this comprehensive review, we summarize the polymorphisms of the main pathogenetic ways involved in AMD development to identify which of them constitutes a potential therapeutic target. As complement overactivation plays a major role, the modulation of targeted complement proteins seems to be a promising therapeutic approach. Herein, we summarize the complement-modulating molecules now undergoing clinical trials, enlightening those in an advanced phase of trial. Gene therapy is a potential innovative one-time treatment, and its relevance is quickly evolving in the field of retinal diseases. We describe the state of the art of gene therapies now undergoing clinical trials both in the field of complement-suppressors and that of anti-VEGF.

Retinal and Corneal Changes Associated with Intraocular Silicone Oil Tamponade.

Silicone oils (SO) are used as long-term intraocular tamponades and have an irreplaceable role in vitreoretinal surgery. They can, however, be associated with multiple and potentially severe complications, involving different ocular tissues, in particular retina and cornea. Recent advances in ophthalmic imaging have allowed the precise characterization of retinal and corneal microstructural changes, at a subclinical level. This detailed analysis of SO-related retinal and corneal changes has improved our understanding of their pathogenesis and offer the potential for optimized monitoring and management of patients with SO-filled eyes. This review aims to provide clinicians and ophthalmic scientists with an updated and comprehensive overview of the corneal and retinal changes associated with SO tamponade.

OCT Analysis of Retinal Pigment Epithelium in Myopic Choroidal Neovascularization: Correlation Analysis with Different Treatments.

Objective: The objective of this study was to analyze the status of the retinal pigment epithelium (RPE) by means of the spectral domain optical coherence tomography (SD-OCT) overlying the myopic neovascular lesions in the involutive phase, looking for any correlations between the status of the RPE and the size of the lesions and the type and duration of the treatment. Methods: SD-OCT examinations of 83 consecutive patients with myopic choroidal neovascularization (CNV) were reviewed and divided into two groups: group A, patients with CNV characterized by uniformity of the overlying RPE, and group B, patients with CNV characterized by non-uniformity of the overlying RPE. Results: The median lesion area, major diameter, and minimum diameter were, respectively, 0.42 mm2 (0.30−1.01 mm2), 0.76 mm2 (0.54−1.28 mm2), and 0.47 mm2 (0.63−0.77 mm2) in group A, and 1.60 mm2 (0.72−2.67 mm2), 1.76 mm2 (1.13−2.23 mm2), and 0.98 mm2 (0.65−1.33 mm2) in group B. These values were lower in group A than in group B (p < 0.001). The number of treatments with a period free of disease recurrence for at least 6 months was greater (p < 0.010) in group B (6.54 ± 2.82) than in group A (3.67 ± 2.08), and treatments include intravitreal anti-vascular endothelial growth factor injection, photodynamic therapy, or both. Conclusions: Our results showed that the size of myopic neovascular lesion influences the development of a uniform RPE above the lesion and therefore the disease prognosis. The presence of uniform RPE was found to be extremely important in the follow-up of patients with myopic CNV, as it influences the duration of the disease and the number of treatments required.

Curcumin in Retinal Diseases: A Comprehensive Review from Bench to Bedside.

Recent evidence in basic science is leading to a growing interest in the possible role of curcumin in treating retinal diseases. Curcumin has been demonstrated to be able to modulate gene transcription and reduce ganglion cell apoptosis, downgrade VEGF, modulate glucose levels and decrease vascular dysfunction. So far, the use of curcumin has been limited by poor bioavailability; to overcome this issue, different types of carriers have been used. Multiple recent studies disclosed the efficacy of using curcumin in treating different retinal conditions. The aim of this review is to comprehensively review and discuss the role of curcumin in retinal diseases from bench to bedside.

Management of refractory and recurrent macular holes: A comprehensive review.

The primary repair of full-thickness macular holes (FTMHs) through pars plana vitrectomy with internal limiting membrane peeling and gas tamponade is the current standard of practice and offers a high closure rate of approximately 90%. On the contrary, the surgical management of refractory (or persistent) and recurrent FTMHs is still a challenging and controversial topic in vitreoretinal surgery as multiple options have been suggested, particularly over the last few years, with no consensus regarding any appropriate selection criteria or the best surgical option. Moreover, the presence of various case series / interventional studies presenting comparable outcomes, as well as the absence of studies with a direct comparison of different surgical techniques, may result in confusion. We provide a structured and comprehensive overview of the different surgical options currently available for the secondary repair of refractory and recurrent FTMHs. In addition to an update on epidemiology, diagnosis and description of the surgical steps, we highlight the evidence available to support each of the described surgical techniques, specifically focusing on the presumed mechanisms of hole closure, advantages, and known prognostic factors.

Short-Term Outcomes After COVID-19-Related Treatment Interruption Among Patients with Neovascular Age-Related Macular Degeneration Receiving Intravitreal Bevacizumab.

PURPOSE: To assess outcomes and recovery strategy of patients undergoing intravitreal injections for exudative age-related macular degeneration who experienced COVID-19 related interruption in treatment during complete lockdown. METHODS: This was a retrospective, observational case study. We used a mixed effect model with random intercepts to evaluate best corrected visual acuity (BCVA) accounting for measured central macular thickness (CMT) and individual variability of each eye. Furthermore, we analysed measures of the pigmented epithelium detachment as well as presence of subretinal fluid and intraretinal cysts. RESULTS: We included 39 patients and we found a significant reduction in the BCVA between the pre- and post-lockdown controlling for CMT. There was no significant difference in pigmented epithelium detachment and in presence of subretinal fluid and intraretinal cysts. CONCLUSION: We detected a significant loss in visual function. The magnitude of the average loss was, however, limited suggesting good efficacy of the recovery strategy.

Outcomes of Abrupt Switch to Bevacizumab of Patients Undergoing Aflibercept Intravitreal Injections for Neovascular Age-Related Macular Degeneration in a Tertiary Center in Lombardy, Italy: A Real-Life Retrospective Analysis.

PURPOSE: To assess real-life anatomical and functional outcomes of switch to bevacizumab in patients undergoing aflibercept intravitreal injections for nAMD. METHODS: Retrospective chart review of all patients diagnosed with nAMD and undergoing intravitreal injections of aflibercept who switched to bevacizumab after the resolution XI/1986 of Lombardy Region. RESULTS: Among 128 patients undergoing intravitreal injections, a total of 29 eyes of 29 patients met all inclusion criteria and were included in the statistical analysis. Best corrected visual acuity and central macular thickness did not change significantly (p > 0.05) between baseline, after the loading phase, and at the last follow-up. CONCLUSION: Switching to bevacizumab has been safe and efficacious in patients responding to the loading phase. According to our results, the restrictions imposed by Lombardy Region did not cause any harm to patients undergoing intravitreal anti-VEGF injections.

Corneal Cross-linking for Progressive Keratoconus in Patients Older Than 40 Years: Long-term Follow-up.

PURPOSE: To assess the long-term efficacy and safety of epithelium-off corneal cross-linking according to the standard (Dresden) protocol (S-CXL) in patients with progressive keratoconus older than 40 years. METHODS: Seventy-six eyes of 64 patients with a mean age of 46.4 ± 5.2 years were included. At baseline and after 6, 12, 24, 36, 48, 60, 72, 84, and more than 96 months (when available) after S-CXL, all patients were assessed with distance-corrected visual acuity (DCVA) and corneal topography and tomography with Pentacam HR (OCULUS Optikgeräte GmbH). A generalized linear model was used to compare the groups. Outcome measures were maximum keratometry, thinnest point, coma, spherical, and higher order aberrations, and ABC values. Fixed and random factors were age, gender, atopy, laterality, and group. RESULTS: The mean follow-up time was 62.1 ± 40.1 months (range: 12 to 144 months). The main outcome of the study was the evidence that S-CXL was able to safely stop the progression of keratoconus in all patients with none requiring repeat CXL. The generalized linear model analysis showed no significant change in DCVA over time (P = 1.000), but atopy was negatively associated with DCVA (P = .030, B = -0.69). The generalized linear model also showed that CXL was able to induce a significant flattening demonstrated as reduction of maximum keratometry (P = .001, B = -0.35) and A value (P =.001, B = -0.015) of the ABC display. Similarly, coma aberration was reduced over time (P = .006, B = -0.005). CONCLUSIONS: S-CXL was confirmed to be a safe and effective treatment for progressive keratoconus even after the age of 40 years, inducing a significant flattening of the cone. [J Refract Surg. 2021;37(5):338-342.].

Optic disc drusen: a systematic review : Up-to-date and future perspective.

BACKGROUND: Optic disc drusen (ODD) are acellular deposits in the prelaminar optic nerve head. The most accredited theory is that they are secondary to abnormalities in axonal metabolism and degeneration, but the pathogenesis is not clear to date. CLINICAL MANIFESTATION: Although ODD are often considered a benign condition, the great majority of patients with ODD show visual field defects and are at higher risk for developing anterior ischemic optic neuropathy. ODD are classified as superficial or buried, with the latter being often misdiagnosed as papilledema with optic nerve head swelling, leading to an unnecessary investigation for causes of increased intracranial pressure. AIM: The recent technological improvements in OCT imaging which allowed an earlier and more certain diagnosis even of the smallest ODD, renovated the interest around this pathology. However, an updated systematic review is still missing. Therefore, the aim of this work is to provide a concise yet comprehensive overview of the current state of art, focusing on pathophysiology, clinical presentation, diagnostic methods, treatment modalities and potential future perspectives of this condition.

Safety of silicone oils as intraocular medical device: An in vitro cytotoxicity study.

This study aimed to assess the cytotoxic effect of low molecular weight components (LMWC) and conventional silicone oils (SOs) 1000 cSt with different degree of purification (raw, intermediate, and purified) using in vitro cytotoxicity tests. Direct contact cytotoxicity tests were performed in BALB 3T3 and human retinal pigment epithelial cells (ARPE-19) using quantitative and qualitative evaluation according to the ISO 10993-5 (2009) standards. Conventional SOs 1000 cSt in form of raw, intermediate (intermediate product obtained during distillation process), and purified SO (final product after distillation) and a concentrate of LMWC (including siloxane chains with molecular weight up to 1557 g/mol) were directly applied to 100% of cell layer area for 24 h. Cell viability was quantified using 3-(4,5-dimethylthiazole-2-yl)-2,5-28 diphenyltetrazolium bromide (MTT) and neutral red uptake assays in ARPE-19 and BALB3T3, respectively. All tested samples, including the concentrate of LMWC, resulted to be not cytotoxic according to ISO 10993-5 in both qualitative and quantitative evaluations. However, the cellular viability was significantly higher in the intermediate and purified SO compared with the raw SO in ARPE-19 cells. No reduction in cell viability was detected by LMWC. The absence of cytotoxicity was observed for all tested samples in both BALB3T3 and ARPE-19 after 24 h of application. A direct cytotoxic effect is not likely to be involved in the potential complications related to SO and LMWC. Long-term potential adverse effects of SO could be related to the raw material and to different concentrations of LMWC.

Curcumin-Based Treatment for Macular Edema from Uncommon Etiologies: Efficacy and Safety Assessment.

The aim of this study was to investigate the efficacy and safety of curcumin formulation with a polyvinylpyrrolidone-hydrophilic carrier (CHC*; Diabec®-AlfaIntes, Italy) for the treatment of macular edema (ME) from uncommon etiologies. We conducted retrospective interventional case series, reviewing the medical records of patients referred to the Eye Center, Humanitas Hospital, Bergamo due to persistent ME related to uncommon causes and treated by oral administration of CHC. The main outcomes assessed were best-corrected visual acuity (BCVA), central macular thickness (CMT), and the presence of intraretinal and/or subretinal fluid (SRF). Only patients with a minimum follow-up (f/u) of 6 months were included. The occurrence of any adverse effect was registered. Thirty-one eyes of 30 patients were included, with a mean f/u of 8.32 ± 1.77 months. Of them, 9 patients (10 eyes) were affected by postoperative ME and 21 by chronic central serous chorioretinopathy. Median BCVA significantly improved after treatment, changing from 0.3 [0.16-0.5] to 0.1 [0-0.3] logarithm of the minimum angle of resolution (P < .001). Also CMT was significantly improved, as it decreased from 400 [364-438] µm before treatment to 280 [242-307] µm at the last f/u visit (P < .001). The complete absorption of intraretinal/SRF was detected in 23 of 31 eyes (74%) at the final f/u. No adverse effects were registered. In conclusion, treatment with CHC was effective and safe for eyes affected by ME of various uncommon etiologies, resulting in significant improvement of both functional and anatomical outcomes, with the complete resolution of the edema in the majority of cases (74%).

The role of different mechanical circulatory support devices and their timing of implantation on myocardial damage and mid-term recovery in acute myocardial infarction related cardiogenic shock.

OBJECTIVES: Aim of the study was to assess in-hospital survival rate and the degree of myocardial recovery after MCS treatment (IABP or IMPELLA) at discharge and at 6 months in patients with AMI-CS and planned early percutaneous revascularization. BACKGROUND: All studies on MCS for acute myocardial infarction related cardiogenic shock (AMI-CS) focused on its impact on in-hospital mortality; however, few data about its role on myocardial recovery are available. METHODS: Retrospective study on 64 patients: 36 patients (56%) received IABP and 28 (44%) Impella 2.5/CP. RESULTS: Patients treated with Impella were sicker compared to those treated with IABP as shown by a higher need of catecholamines (93% Impella vs 57% IABP, P = 0.002) and higher inotropic score before procedure: 8 (5-15) versus 4.5 (0-9), P = 0.02. In-hospital survival and MCS-related complications were comparable; hemolysis was more frequent in the Impella group (32% vs 0%, P < 0.0001). Myocardial damage was lower in those patients who were implanted with IMPELLA before PCI: lower troponin peak [3831 ng/dL (1441-8436) vs 16 581 (7802-23 675), P = 0.004] and lower CPK peak [893 UI/L (584-4082) vs 5797 (2483-9292) P = 0.04]. Impella patients had higher LVEF at 6 months [45 (38-52) vs 40 (33-45)%, P = 0.04]. LVEF increase at 6 months was statistically significant in both groups (P < 0.0001), with higher myocardial recovery in patients supported with Impella (absolute delta-LVEF increase 20% vs 10% P = 0.005). CONCLUSIONS: Cardiac unloading with IMPELLA in ACS-CS, especially if implanted before PCI, might provide lower myocardial damage and improved myocardial recovery which translates into significantly higher LVEF at 6 months.