Intravitreal Brolucizumab for Pachychoroid Neovasculopathy Associated With Chronic Central Serous Chorioretinopathy.

Purpose: To evaluate the anatomical and functional outcomes of intravitreal brolucizumab in eyes with chronic central serous chorioretinopathy complicated by pachychoroid neovasculopathy. Methods: Retrospective analysis of 34 eyes treated with intravitreal brolucizumab. Twenty-five eyes (73.5%) had been treated with other anti-vascular endothelial growth factor agents before switching to brolucizumab, whereas nine eyes were naïve. Outcome measures included the change of central foveal thickness and subfoveal choroidal thickness, evaluation of sub/intraretinal fluid on optical coherence tomography, and change in best-corrected visual acuity. Results: Before starting brolucizumab, 23 eyes showed subretinal fluid, 8 both subretinal and intraretinal fluid, and 3 intraretinal fluid only. At the last visit, 22 eyes (64.7%) showed complete reabsorption of both intraretinal and subretinal fluid, whereas subretinal fluid was still present in 8 eyes (23.5%), and both intraretinal and subretinal fluid in 4 eyes (11.8%). The mean number of brolucizumab injections required to achieve complete fluid reabsorption was 2.8 ± 1.8. central foveal thickness decreased from 317.8 ± 109.3 µm to 239.8 ± 74.8 µm (P = 0.0005) and subfoveal choroidal thickness decreased from 399.3 ± 86.2 µm to 355.5 ± 92.7 µm at the end of the follow-up period (P = 0.0008). The mean logarithm of the minimum angle of resolution best-corrected visual acuity improved from 0.4 ± 0.2 to 0.3 ± 0.2 at 1 month after the first injection and remained stable at the same values at the end of the follow-up period (P = 0.04). Conclusions: Intravitreal brolucizumab is effective for the treatment of naïve and recalcitrant pachychoroid neovasculopathy. Translational Relevance: Intravitreal brolucizumab may represent an option in patients with pachychoroid neovasculopathy complicating chronic central serous chorioretinopathy.

Pathophysiology, Functional Assessment and Prognostic Implications of Nutritional Disorders in Systemic Amyloidosis.

Gastrointestinal involvement is a common clinical feature of patients with systemic amyloidosis. This condition is responsible for invalidating gastrointestinal symptoms, a significant macro and micronutrient deficit, and is a marker of disease severity. Gastrointestinal involvement should be actively sought in patients with systemic amyloidosis, while its diagnosis is challenging in patients with isolated gastrointestinal symptoms. The nutritional status in systemic amyloidosis plays an essential role in the clinical course and is considered a significant prognostic factor. However, the definition of nutritional status is still challenging due to the lack of internationally accepted thresholds for anthropometric and biochemical variables, especially in specific populations such as those with systemic amyloidosis. This review aims to elucidate the fundamental steps for nutritional assessment by using clinical and instrumental tools for better prognostic stratification and patient management regarding quality of life and outcomes.

OCT angiography indices and the choroidal vascularity index in wild-type transthyretin (TTR) amyloidosis (ATTRwt).

Purpose: Retinal angiopathy represents a well-known ocular manifestation of hereditary transthyretin amyloidosis (ATTRv). Until recently, there have been no reports on retinal changes in ATTRwt. In this retrospective observational clinical study, we aimed to determine whether vessel density (VD) indices and the choroidal vascularity index (CVI) could offer insights into retinal and choroidal vascular changes among patients affected by ATTRwt. Methods: Eighteen patients with a confirmed diagnosis of ATTRwt underwent structural optical coherence tomography (OCT) and OCT angiography (OCTA). We established a control group consisting of 16 healthy subjects for statistical comparisons. The 3D OCT and OCTA datasets were analyzed to assess retinal and choroidal thickness and VD. For measuring CVI, we obtained measurements for the total choroid area (TCA), luminal area (LA), and stromal area (SA). Results: The mean VD exhibited a statistically significant reduction in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choriocapillaris (CC) among the ATTRwt group in comparison to the control group (p < 0.0001). Notably, ATTRwt patients displayed decreased choroidal thickness (p = 0.08). Additionally, the median CVI was lower in the ATTRwt group than in the control group (p = 0.04). Conclusion: The indices from OCTA and CVI have the potential to serve as non-invasive biomarkers for the quantitative evaluation of retinal and choroidal vascular involvement in patients with ATTRwt.

An Overview of Molecular Mechanisms in Fabry Disease.

Fabry disease (FD) (OMIM #301500) is a rare genetic lysosomal storage disorder (LSD). LSDs are characterized by inappropriate lipid accumulation in lysosomes due to specific enzyme deficiencies. In FD, the defective enzyme is α-galactosidase A (α-Gal A), which is due to a mutation in the GLA gene on the X chromosome. The enzyme deficiency leads to a continuous deposition of neutral glycosphingolipids (globotriaosylceramide) in the lysosomes of numerous tissues and organs, including endothelial cells, smooth muscle cells, corneal epithelial cells, renal glomeruli and tubules, cardiac muscle and ganglion cells of the nervous system. This condition leads to progressive organ failure and premature death. The increasing understanding of FD, and LSD in general, has led in recent years to the introduction of enzyme replacement therapy (ERT), which aims to slow, if not halt, the progression of the metabolic disorder. In this review, we provide an overview of the main features of FD, focusing on its molecular mechanism and the role of biomarkers.

Optical Coherence Tomography Angiography Analysis of Vessel Density Indices in Early Post-COVID-19 Patients.

Purpose: A hypercoagulable state has been reported to cause potential sight-threatening ischemia in patients suffering from Coronavirus disease 2019 (COVID-19). This study aimed to determine whether vessel density (VD), as measured by optical coherence tomography angiography (OCT-A), has insights into retinal and choriocapillaris vascular changes in patients affected by SARS-CoV-2 infection. Methods: Hundred and fifty two patients positive for SARS-CoV-2 infection were enrolled in this observational, retrospective, controlled study. A control group of 60 healthy subjects was selected for statistical comparisons. Raw OCT and OCT-A data were exported and 3D datasets were analyzed to determine VD. Results: Hundred and forty eyes (92.1%) were included for final analysis. The VD of the superficial capillary plexus (SCP) did not differ between the two groups. The mean VD of the deep capillary plexus (DCP) and the choriocapillaris (CC) was significantly lower in the foveal sector of the COVID-19 group compared to healthy controls. Within the post-COVID-19 group, the lowest DCP and CC foveal VD values were recorded in patients treated with antiviral therapy; no differences were observed among COVID-19 patients with other comorbidities (hypertension, diabetes, thyroid disease) or taking antiplatelet therapy. DCP and CC foveal VD were significantly lower in patients hospitalized in an intensive care unit (ICU) than asymptomatic patients. Conclusion: Foveal vessel density at the level of DCP and CC was reduced in post-COVID-19 patients. Further studies evaluating these changes over time will be needed to corroborate the hypothesis of a microvascular retinal impairment in individuals who have recently recovered from SARS-CoV-2 infection.

Effect of a Fixed Combination of Curcumin, Artemisia, Bromelain, and Black Pepper Oral Administration on Optical Coherence Tomography Angiography Indices in Patients with Diabetic Macular Edema.

Background: To investigate the effects of a fixed combination of Curcumin (200 mg), Artemisia (80 mg), Bromelain (80 mg), and Black pepper (2 mg) on vascular parameters in mild to moderate diabetic macular edema (DME). Design: Prospective, case-control study. Methods: Fifty-six patients affected by diabetes mellitus type II were enrolled in the study. Twenty-eight patients with DME received 2 tablets/day, before meals of a dietary complementary supplement containing in fixed combination Curcumin (200 mg), Artemisia (80 mg), Bromelain (80 mg), and Black pepper (2 mg) (Intravit®, OFFHEALTH Spa, Firenze, Italy) for 6 months. Twenty-eight age-matched subjects affected by diabetes mellitus type II were given placebo and served as control group. Patients underwent best correct visual acuity (BCVA), swept optical coherence tomography (OCT), and OCT-Angiography (OCTA). OCTA images of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) were obtained for each eye. By the end of the follow-up patients were defined responder to the therapy when a decrease of more than 30 µm was registered in central retinal thickness (CRT) measurement, while a poor responder was determined by the absence of reduction or an increase in central retinal thickness at 6 months. We assessed the foveal avascular zone (FAZ) area, vessel density and quantified the number of microaneurysms in each layer. Results: A significant improvement of BCVA and CRT reduction was recorded at 6 months follow-up in the dietary complementary supplementation group compared to control (respectively p = 0.028 and p = 0.0003). VD of the total capillary plexus, microaneurysms count, glycaemia and HbA1c did not vary over the follow-up period between groups. Within the Intravit® group, poor responders tended to show a larger FAZ area, more microaneurysms, and a lower VD in the DCP compared to the good responders group (p < 0.0001). Conclusions: A fixed combination of Curcumin, Artemisia, Bromelain, and Black pepper oral administration may have a positive impact on central retinal thickness, visual acuity, and VD of the DCP in compensated type 2 diabetic patients with mild DME.

The Heart Muscle and Valve Involvement in Marfan Syndrome, Loeys-Dietz Syndromes, and Collagenopathies.

The inherited connective tissue disorders (Marfan syndrome, Loeys-Dietz syndrome [LDS], and Ehlers-Danlos syndrome [EDS]) involve connective tissue of various organ systems. These pathologies share many common features, nonetheless compared to Marfan syndrome, LDS' cardiovascular manifestations tend to be more severe. In contrast, no association is reported between LDS and the presence of ectopia lentis. The EDS are currently classified into thirteen subtypes. There is substantial symptoms overlap between the EDS subtypes, and they are associated with an increased incidence of cardiovascular abnormalities, such as mitral valve prolapse and aortic dissection.

Diagnosis and Management of Cardiovascular Involvement in Fabry Disease.

Fabry disease (FD, OMIM 301500) is an X-linked lysosomal storage disease caused by pathogenic variants in the GLA gene. Cardiac involvement is common in FD and is responsible for impaired quality of life and premature death. The classic cardiac involvement is a nonobstructive form of hypertrophic cardiomyopathy, usually manifesting as concentric left ventricular hypertrophy, with subsequent arrhythmogenic intramural fibrosis. Treatment of patients with FD should be directed to prevent the disease progression to irreversible organ damage and organ failure. The aim of this review is to describe the current state of knowledge regarding cardiovascular involvement in FD, focusing on clinical and instrumental features, cardiovascular management, and targeted therapy.

Unintentional Retinal Displacement in Eyes Treated for Rhegmatogenous Retinal Detachment Complicated by Proliferative Vitreoretinopathy with Pars Plana Vitrectomy and Silicone Oil.

PURPOSE: To examine the clinical characteristics, outcomes, and rate of unintentional displacement in eyes treated for rhegmatogenous retinal detachment (RRD) with pars plana vitrectomy (PPV) and silicone oil (SO). METHODS: This retrospective observational study examined 50 eyes of 50 patients who underwent surgical repair for primary RRD complicated by proliferative vitreoretinopathy (PVR) by PPV and 1000-centistoke SO injection at a single institutional centre. The patients assumed a face-down posture immediately after surgery. Blue-fundus autofluorescence (B-FAF) pictures were obtained at 1 month after surgical procedures using a Spectralis HRA + OCT (Heidelberg Engineering, Heidelberg, Germany). RESULTS: The primary success rate was obtained in 44 eyes (88%), on which the final analysis was conducted. Preoperative PVR was grade A in 7 eyes (15.9%), grade B in 28 eyes (63.6%), and grade C in 9 eyes (20.5%). The fovea was off and the detachment involved both the superior and inferior hemispheres of the retina in all cases. Breaks were located in the upper quadrants in 19 eyes (43.2%), in the lower quadrants in 12 eyes (27.3%), and in both upper and lower quadrants in 13 eyes (29.5%). The mean number of breaks was 3.4 ± 1.9. Intraoperative PFCL was used in 30 eyes (68.2%). Peeling of the epiretinal membrane/internal limiting membrane in the macula area was performed in 13 eyes (29.5%) during the first operation and carried out in all other eyes in occasion of SO removal. Preoperative BCVA was 2.1 ± 1.0 logMAR and improved to 0.8 ± 0.7 logMAR at the last follow-up (P < 0.0001). An upward unintentional retinal displacement was observed in 2 cases (4.5%). CONCLUSION: PPV and SO tamponade for complicated RRD are associated with good anatomical and functional outcomes and a very low rate of unintentional retinal displacement. Of the factors potentially implicated in favouring displacement that were studied, none were found significant.

The retinoprotective role of phenytoin.

Phenytoin is a non-sedative barbiturate derivate and has been recently rediscovered as a neuroprotective and retinoprotective compound in patients affected by optic neuritis secondary to multiple sclerosis. However, currently there are still no neuroprotective compounds registered and available in the clinic. We reviewed the literature supporting the retinoprotective properties of phenytoin and analyzed the various approaches and definitions from the first research periods onwards. The retinoprotective role of phenytoin was already known in the 1970s, but only recently has this effect been rediscovered, confirming that it could indeed provide structural protection of the retinal cells.

Cytoprotective Effects of Citicoline and Homotaurine against Glutamate and High Glucose Neurotoxicity in Primary Cultured Retinal Cells.

Citicoline and homotaurine are renowned compounds that exhibit potent neuroprotective activities through distinct molecular mechanisms. The present study was undertaken to demonstrate whether cotreatment with citicoline and homotaurine affects cell survival in primary retinal cultures under experimental conditions simulating retinal neurodegeneration. Primary cultures were obtained from the retina of fetal rats and exposed to citicoline plus homotaurine (100 µM). Subsequently, neurotoxicity was induced using excitotoxic levels of glutamate and high glucose concentrations. The effects on retinal cultures were assessed by cell viability and immunodetection of apoptotic oligonucleosomes. The results showed that a combination of citicoline and homotaurine synergistically decreases proapoptotic effects associated with glutamate- and high glucose-treated retinal cultures. This study provides an insight into the potential application of citicoline and homotaurine as a valuable tool to exert neuroprotective effects against retinal damage.

Resolvins and aliamides: lipid autacoids in ophthalmology - what promise do they hold?

Resolvins are a novel class of lipid-derived endogenous molecules (autacoids) with potent immunomodulating properties, which regulate the resolution phase of an active immune response. These modulating factors are locally produced, influencing the function of cells and/or tissues, which are produced on demand and subsequently metabolized in the same cells and/or tissues. This review is focused on certain lipid autacoids with putative relevance for ophthalmology in general and for dry eye more specifically. We also briefly investigate the concept of aliamides and the role of palmitoylethanolamide in ophthalmology, and analyze in more detail the putative role and the preclinical and clinical development of resolvins as emerging treatments for dry eye and related disorders, with a focus on one of the lead resolvin derivatives - RX-10045.

TREATMENT OF EXUDATIVE AGE-RELATED MACULAR DEGENERATION WITH RANIBIZUMAB COMBINED WITH KETOROLAC EYEDROPS OR PHOTODYNAMIC THERAPY.

PURPOSE: To evaluate whether ketorolac eyedrops plus intravitreal ranibizumab (IVR) or verteporfin photodynamic therapy plus IVR provides additional benefit over IVR monotherapy for treatment of choroidal neovascularization in age-related macular degeneration. METHODS: This was a prospective, randomized, pilot study in 75 patients with naive choroidal neovascularization. Patients were randomized 1:1:1 into 3 groups: ranibizumab monotherapy (RM), ranibizumab plus ketorolac, or ranibizumab plus loading-phase reduced-fluence verteporfin photodynamic therapy (RV) groups. RESULTS: At 12 months, all groups showed significant improvement in both best-corrected visual acuity and central retinal thickness. The mean best-corrected visual acuity change from baseline to 12 months was -0.14 ± 0.52 logMAR (20/73 ± 20/29), -0.25 ± 0.60 logMAR (20/46 ± 20/27), and -0.10 ± 0.30 (20/97 ± 20/40) logMAR in RM, ranibizumab plus ketorolac, and RV groups, respectively. The mean central retinal thickness change from baseline to 12 months was -125 ± 15 µm, -141 ± 21 µm, and -130 ± 15 µm in RM, ranibizumab plus ketorolac, and RV groups, respectively. Both ranibizumab plus ketorolac and RV groups required fewer IVR treatments than RM. CONCLUSION: Compared with RM and ranibizumab plus verteporfin photodynamic therapy, the combination of 0.45% ketorolac eyedrops 3 times a day and ranibizumab in patients with choroidal neovascularization provided superior best-corrected visual acuity and central retinal thickness outcomes. Both combination regimens required fewer IVR injections than RM during the 12-month follow-up period.

Intravitreal pegaptanib sodium (Macugen) for treatment of myopic choroidal neovascularization: a morphologic and functional study.

BACKGROUND: To report the morphologic and functional outcomes resulting from the use of intravitreal pegaptanib (IVP) sodium (Macugen) in patients with myopic choroidal neovascularization. METHODS: An open-label, nonrandomized, prospective clinical trial was performed. Morphologic outcome, such as foveal thickness, was assessed by optical coherence tomography, whereas functional outcomes were assessed by best-corrected visual acuity and microperimetry. Treatment protocol consisted of 3 consecutive IVP (0.3 mg/0.05 mL; baseline, 6th week, and 12th week). Follow-up checks were scheduled at the following intervals: baseline, 18, 24, 36, and 48 weeks. RESULTS: Twenty eyes from 20 patients were studied. All patients completed follow-up at 48 weeks. After IVP, a significant decrease in foveal thickness occurred (-20%), and at the end of follow-up, choroidal neovascularization closure was obtained in all eyes. An improvement of functional parameters was recorded in all patients (best-corrected visual acuity from 25.5 ± 8.09 letters to 45.5 ± 8.16 letters, P < 0.0001; microperimetry from 8.40 ± 2.14 dB to 10.8 ± 2.05 dB, P < 0.01). The mean number of IVP was 3, and none of patients met the re-treatment criterion during the entire follow-up period. Neither ocular nor systemic side effects were observed. CONCLUSION: The findings demonstrate that the selective inhibition of VEGF-165 isoform by IVP is an effective treatment for myopic choroidal neovascularization.

Intravitreal pegaptanib sodium (Macugen®) for treatment of diabetic macular oedema: a morphologic and functional study.

AIMS: To study whether morphologic (foveal thickness, FT) variations of clinically significant macular oedema (CMO) in patients suffering from diabetes following intravitreal pegaptanib sodium (IVP) injection were associated with functional [macular sensitivity (MS) and colour discrimination (CD)] changes. METHODS: A longitudinal, interventional, non-randomized study was performed. FT was assessed by optical coherence tomography (OCT), MS by microperimetry, best-corrected visual acuity (BCVA) by early treatment diabetic retinopathy study charts (ETDRS) and CD by Farnswoth-Munsell test. The treatment protocol consisted of three consecutive injections (0.3 mg/0.05 ml; baseline, week 6 and week 12). Follow-up checks were scheduled at 18, 24, 36 and 48 weeks, after injections. RESULTS: Thirty eyes of 30 patients with clinically significant CMO were included for analysis. After IVP a significant decrease of FT occurred with a mean reduction from baseline of 56.9% (P= 0.0001). An improvement of functional parameters was recorded in all patients (BCVA from 18.2 ± 8.5 letters to 25.5 ± 8.4 letters, P < 0.005, MS from 8.6 ± 2.16 dB to 10.6 ± 2.61 dB, P < 0.001, colour analysis from 376.1 ± 125.6 TES to 116 ± 34.6 TES, P= 0.0001). A statistically significant correlation between FT and BCVA as well as MS and CD was also found. Neither ocular nor systemic adverse events were reported. CONCLUSIONS: Intravitreal pegaptanib significantly reduced FT, with a concomitant improvement of MS and CD. This association emphasizes the efficacy of IVP in the treatment of CMO.

Ocular manifestations in hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease): a case-series.

BACKGROUND: Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) is an autosomal dominant vascular disorder characterized by severe and recurrent nosebleeds, muco-cutaneous telangiectasias, and, in some cases, life-threatening visceral arteriovenous malformations. Ocular abnormalities include conjunctival telangiectasia, arteriovenous fistula, angiectasia, phlebectasia, and angioma. MATERIAL AND METHODS: We describe the ocular abnormalities in 8 patients from a pedigree with hereditary hemorrhagic telangiectasia. This article also reviews and discusses the relevant literature. RESULTS: Five patients (62.5%) had conjunctival telangiectasias and 3 (37.5%) retinal abnormalities, consisting mainly of choriocapillaris atrophy. CONCLUSIONS: To the best of our knowledge, this is the first report describing the occurrence of choriocapillaris atrophy in patients affected by hereditary hemorrhagic telangiectasia and belonging to the same pedigree.

Low fluence rate photodynamic therapy combined with intravitreal bevacizumab for neovascular age-related macular degeneration.

AIMS: To report the efficacy and safety of intravitreal bevacizumab (IVB) alone versus IVB plus low-fluence photodynamic therapy (PDT) in age-related macular degeneration (AMD) patients and to verify the occurrence of a synergistic effect of the combined approach on visual acuity, size and morphology of lesion, as well as on the treatment rate. METHOD: Prospective comparative interventional study on 85 patients with treatment-naive classic, or predominantly classic, subfoveal choroidal neovascularisation secondary to AMD. Patients were randomly assigned to group 1 (IVB injections) and group 2 (IVB plus low fluence PDT). In group 2, the PDT with verteporfin was delivered with a low fluence rate (300 mW/cm2 for 83 s, 25 J/cm2). The follow-up was scheduled at 1, 3, 6, 9 and 12 months. RESULTS: The eye without recurrence received a mean of 2.8 (group 1) versus 1.4 (group 2) IVB injections, whereas the eyes with recurrence received a mean of 3.2 (group 1) versus 2.2 (group 2) IVB injections. The difference in reinjection rate between the two groups was statistically significant (p=0.03, ANOVA test). Visual acuity improvement was not statistically significant between the two groups (p=0.31). CONCLUSION: The combination of IVB with low fluence PDT for the treatment of classic or predominantly classic neovascular AMD works in a synergistic fashion with a significant reduction in IVB reinjections rate.

Retinal phototoxicity induced by hydrochlorothiazide after exposure to a UV tanning device.

UV radiation is known to cause acute and chronic eye and skin damage. The present case report describes the occurrence of hydrochlorothiazide-induced retinal phototoxicity immediately after exposure to UV light emanated from a sunbed in a 40-year-old myopic woman. During the tanning session she had always worn UV protective eyewear, except for a few minutes when she took the protective goggles off to put her spectacles on to locate and turn the timer switch off. At baseline her visual acuity was 10/25 in OD and 10/80 in OS. Fundus examination revealed the presence of retinal lesions in both eyes. More specific tests confirmed the presence of a phototoxic macular damage. Hydrochlorothiazide was discontinued, and she was recommended to wear UV filtering glasses. Over the follow-up period (12 months), a slow and progressive visual acuity recovery in both eyes occurred. At the last check the visual acuity improvement was of about 60% from baseline in both eyes. Fundus examination showed only a juxtafoveal flat pigmented scar of the retinal pigment epithelium in both eyes, milder in OD. The constant rise in the number of sunbed users makes the knowledge of UV-related side effects a problem that cannot be postponed further. Awareness of the general public about the harmful effects of UV exposure must represent one of the leading preventive health strategies. Therefore, a careful analysis of the medical history before the admission to a sunbed session throughout a questionnaire could represent an economic and effective measure to avoid further cases of a phototoxic macular damage in patients taking photosensitizing compounds.