Effects of circadian rhythm disruption on retinal physiopathology: Considerations from a consensus of experts.

The circadian rhythms originate within the organism and synchronize with cyclic fluctuations in the external environment. It has been demonstrated that part of the human genome is under control of the circadian clock and that a synchronizer that helps to maintain daily rhythms is Melatonin, a neuro-hormone primarily synthesized by the pineal gland during the night. The chronic disruption of circadian rhythm has been linked to many conditions such as obesity, metabolic syndrome, type 2 diabetes, cancer, and neurodegenerative diseases. Studies in the mice showed that the disruption of the retinal circadian rhythm increases the decline during the aging of photoreceptors, accelerating age-related disruption of cone cell structure, function, and viability and that the melatonin receptor deletion seems to influence the health of retinal cells, speeding up their aging. In conclusion, preserving the circadian rhythms could be to add to the prevention and treatment of age-related degenerative retinal diseases, and although additional studies are needed, melatonin could be a valid support to favor this "chronoprotection action".

Outer retina dysfunction and choriocapillaris impairment in type 1 diabetes.

To study the outer retina morpho-functional characteristics and the choriocapillaris (CC) features in type 1 diabetic (T1D) patients, with and without signs of diabetic retinopathy (NPDR and NoDR). Twenty-five NPDR and 18 NoDR eyes were imaged by Optical Coherence Tomography Angiography. Ellipsoid zone (EZ) "normalized" reflectivity and CC perfusion density parameters, as flow deficits number (FDn), flow deficit average area (FDa) and flow deficit percentage (FD%), were analysed. Multifocal electroretinogram (mfERG) response amplitude densities (RADs) were measured. Mean EZ "normalized" reflectivity, CC FDn and FD% values, were similar (p > 0.05) in both groups, FDa was significant greater (p > 0.05) in NPDR compared with NoDR eyes. MfERG-RADs were similar in both groups. NPDR eyes showed a significant (p < 0.05) linear correlation between RADs and both, CC FDa and FD%. The EZ "normalized" reflectivity was negatively correlated with CC FD% in NoDR eyes. In NPDR T1D eyes a significant relationship between abnormal outer retina functional responses and CC impairment was observed, while in NoDR eyes the photoreceptor reflectivity was correlated to CC abnormalities. The outer retina dysfunction in NPDR correlated to CC drop-out let hypothesize that the outer retinal elements are functionally impaired in proportion to the CC vascular supply deficit.

MRI characteristics of adductor longus lesions in professional football players and prognostic factors for return to play.

PURPOSE: To correctly define through Magnetic Resonance Imaging (MRI), diagnosis, staging and prognosis of the adductor longus (AL) acute lesions and to identify a correlation between Return to Play (RTP) and sport-related injury predisposing conditions and complications. MATERIALS AND METHODS: Twenty professional football players with acute groin pain and clinical suspicion of AL injury subsequent to sport's activity were evaluated. MRI examinations were performed by one and reviewed by other two radiologists with more than 10 years of experience. Lesions were stratified according to both Munich consensus statement and British Athletics Muscle Injury Classification (BAMIC). Patients were monitored until clinical recovery occurred. RESULTS: According to the Munich consensus statement, 75% of lesions were defined as type 3 and 25%as type 4; while according to the BAMIC, 45% were considered as Grade 1, 20% as Grade 2, 10% as Grade 3, and 25% as Grade 4. RTP was 1-2 weeks for minor lesions (45%), 4-6 weeks for moderate lesions (30%), and more than 6 weeks for complete lesions (25%). Both BAMIC and Munich consensus significantly correlated with RTP (R = 0.958 and 0.974, respectively). The extent of gap was the only independent prognosticator of RTP always present in all three different models of multivariate analysis (p < 0.006, p < 0.002, and p < 0.001, respectively). CONCLUSIONS: MRI represents the gold standard imaging technique for the evaluation of AL due to its ability not only to recognize but also to classify acute lesions and define patient's prognosis. MRI is also useful to detect potential predisposing conditions and complications, which may correlate with RTP.

Response of central serous chorioretinopathy evaluated by multimodal retinal imaging.

PurposeTo identify predictive biomarkers of treatment outcomes by multimodal retinal imaging in patients affected by central serous chorioretinopathy (CSC).Patients and methodsIn this interventional non-randomized clinical study, 27 treatment-naive CSC patients were prospectively enrolled and treated with oral eplerenone for 5-13 weeks. Primary outcomes included presence of pathological findings on indocyaine green angiography (ICGA), structural optical coherence tomography (OCT) and OCT-angiography (OCT-A) at baseline associated with different response to the treatment.ResultsA total of 29 eyes of 27 patients (2 females, 25 males) met the inclusion criteria and were included in the study (mean age was 45±7 years). Mean CSC duration at baseline was 13.5±4.4 weeks. After a mean of 10.5 weeks of treatment, mean central macular thickness significantly reduced (P<0.001), and mean best-corrected visual acuity improved (P<0.001). Seventeen eyes (61%) demonstrated total reabsorption of subretinal fluid on structural OCT, five eyes (18%) presented a partial response to eplerenone therapy and six eyes (21%) showed no response. The complete response to the treatment was associated with absence of CNV at OCT-A and the presence of hotspot at ICGA (P<0.001 and P=0.002, respectively). None of eight eyes with CNV in OCT-A imaging had a complete response to eplerenone and none of three eyes without hotspot at ICGA showed a complete response to the treatment.ConclusionsMultimodal retinal imaging allowed us to propose predictive biomarkers (ie, absence of CNV on OCT-A and presence of hotspot on ICGA) for treatment outcomes.

Multimodal retinal imaging in central serous chorioretinopathy treated with oral eplerenone or photodynamic therapy.

PurposeTo correlate function and structural optical coherence tomography (OCT) to optical coherence tomography angiography (OCT-A) measures in patients affected by central serous chorioretinopathy (CSC) and to describe their changes after treatments (ie oral eplerenone, half-fluence photodynamic therapy (PDT)).Patients and methodsTwenty eyes of 16 consecutive patients with treatment-naïve CSC undergoing either eplerenone or PDT were enrolled in this prospective, observational study. All patients underwent structural OCT and OCT-A at baseline and after therapy at months 1 and 3.ResultsEleven eyes of nine patients and nine eyes of seven patients underwent eplerenone or PDT treatment, respectively. Central macular thickness (CMT) and subretinal fluid (SRF) correlated to fovea avascular zone (FAZ) area (r=0.74 and r=0.71, P=0.01) and vessel density (r=0.77 and r=0.68, P=0.01) at deep capillary plexus (DCP). CMT (P=0.0011), SRF (P=0.0005), SFCT (P=0.0016), FAZ area at DCP (P=0.0334) improved at 3-month visit. A significant reduction of deep FAZ area was appreciated in eplerenone (P=0.0204) but not in PDT (P=0.5) group. SFCT reduction was significantly higher in PDT than eplerenone group (P=0.0347).ConclusionStructural and vascular parameters are correlated in CSC and they improve after different treatments. Both half-fluence PDT and oral eplerenone do not permanently damage choriocapillaris or other choroidal layers as evaluated by OCT-A.

Fundus autofluorescence in retinal artery occlusion: A more precise diagnosis.

IMPORTANCE: Retinal artery occlusion (RAO) is a medical emergency associated with a high risk of cerebral vascular accident and other cardiovascular events. Among patients with non-arteritic RAO, a retinal embolus is observed in approximately 40% of cases. Fundus examination and retinography are not reliable to predict the nature of the emboli. OBSERVATIONS: We report three consecutive cases of central and branch RAO that were investigated with fundus autofluorescence, fluorescein angiography and color retinal photographs. All patients underwent complete neurological and cardiovascular workups, with brain imaging, cardiac Doppler ultrasound, carotid Dopplers and Holter ECG's, to determine the underlying mechanism of retinal embolism. In the three cases, aged 77.7±4 years (2 women and 1 man), fundus autofluorescence demonstrated hyperautofluorescent emboli. In two cases, it allowed visualization of emboli that were not detected with fundus examination or retinography. The cardiovascular work-up demonstrated atheromatous carotid or aortic plaques in all patients. In one case, it permitted the diagnosis of RAO. Two of the three cases were considered to be of atherosclerotic origin and one of undefined origin. CONCLUSION AND RELEVANCE: Fundus autofluorescence may help to detect and characterize retinal emboli. Since lipofuscin, which is present in large quantity in atherosclerotic plaques, is the main fluorophore detected with fundus autofluorescence, this non-invasive and simple examination may give information about the underlying mechanism of retinal embolism, and thus impact the etiologic assessment of RAO. Additional studies are necessary to confirm this potential role of autofluorescence.

MRI detection of soleus muscle injuries in professional football players.

OBJECTIVES: To describe magnetic resonance imaging (MRI) characteristics of soleus muscle injuries in symptomatic professional football players stratified according to both the Munich consensus statement and the British Athletics Muscle Injury Classification (BAMIC), and to investigate the association between specific MRI features and the "return to play" (RTP). MATERIALS AND METHODS: Professional football players with an episode of acute posterior calf pain and impaired function, subsequent to sports activity, underwent ultrasound followed by MRI examination reviewed by two different radiologists with more than 10 years of experience in the musculoskeletal system. MRI features and RTP outcome were evaluated for all types of injuries. RESULTS: During a 36-month period, a total of 20 professional football players were evaluated. According to the Munich consensus, 11 were type 3A, 8 were type 3B, and 1 was type 4, whereas according to the BAMIC, 11 lesions were considered grade 1, 4 grade 2, 4 grade 3, and 1 grade 4. RTP data were available for all patients (mean 3.3 ± 1.6 weeks). Both the Munich consensus and the BAMIC correlated with RTP (Spearman correlation = 0.982 and p < 0.0001 and 0.886 and p < 0.0001 respectively). Extension of edema was an independent prognostic factor for RTP in two different models of multivariate regression analysis (p = 0.044 model A; p = 0.031 model B). CONCLUSIONS: The Munich consensus and BAMIC grading systems are useful tools for defining the patient's prognosis and proper rehabilitation time after injury. The MRI feature that we should carefully look for is the extension of edema, as it seems to significantly affect the RTP.

Optical coherence tomography analysis of evolution of Bruch's membrane features in angioid streaks.

PurposeTo describe optical coherence tomography (OCT) features in the Bruch's membrane (BM) of eyes with angioid streaks (AS) and evaluate their evolution over the follow-up.Patients and methodsPatients with AS presenting between March 2016 and September 2016 at two tertiary referral centers were consecutively recruited in this study. Eligibility criteria included prior spectral domain (SD)-OCT images, taken at least 3 months before at the same referral center, with automated eye tracking and image alignment modules. Alterations of BM were described and compared to previous scans over the follow-up. Multimodal imaging was used to identify alteration of retinal pigment epithelium (RPE) and choroid.ResultsThirty-two eyes of 16 consecutive patients with AS were included. BM undulations, mostly observed around the optic nerve head, were found in 19 (59.4%) of 32 eyes. BM breaks were found in 31 (96.9%) out of 32 eyes. Evolution of BM undulations into BM breaks was observed in 5 eyes (15.6%). Choroidal neovascularization (CNV) was observed in 12 eyes (37.5%) during follow-up, typically in areas of BM interruption.ConclusionsBM undulations, probably caused by high stretching forces exerted on the BM around the optic nerve head, seem to precede some BM breaks. BM interruptions may be a preferred way for the growth of CNV, which was identified in one-third of our cases.

Optical Coherence Tomography Angiography of Diabetic Retinopathy.

PURPOSE: To describe the optical coherence tomography angiography (OCTA) features of diabetic retinopathy. METHODS: Literature review and case series. RESULTS: Four cases are presented. CONCLUSION: OCTA is an effective method for evaluating retinal changes in diabetic retinopathy and represents a novel complement or alternative to fluorescein angiography. Although OCTA should currently be considered an investigational technique, in the near future, it may play key roles in the diagnosis and management of diabetic retinopathy.

Spontaneous retinal pigment epithelium tear in geographic atrophy.

PURPOSE: To report two cases of spontaneous retinal pigment epithelial (RPE) tears occurring in two patients affected with geographic atrophy (GA) due to non-exudative age-related macular degeneration (AMD). CASE REPORT: Two patients (a 79-year-old man and a 71-year-old woman) presented to our department with progressive visual loss. The man had a best-corrected visual acuity (BCVA) of 20/100 in the right eye (RE) and 20/50 in the left eye (LE); the woman had a BCVA of 20/200 in the RE and 20/160 in the LE. Upon complete ophthalmologic examination, revealing a large area of atrophy (>175 µm in diameter) along with pigmentary changes, calcified drusen and no choroidal neovascularization (CNV) in either eye, the patients were diagnosed with GA due to non-exudative AMD. Interestingly, the imaging modalities performed, including fluorescein angiography (FA), indocyanine green angiography (ICGA) and spectral-domain optical coherence tomography (SD-OCT), clearly highlighted the presence of spontaneous RPE tears in the context of non-exudative AMD, while in general, RPE tears are a well-recognized complication of exudative AMD. CONCLUSIONS: To our knowledge, this is the first description of spontaneous RPE tears as a possible complication of GA due to non-exudative AMD.