Predictors of 24-month onset of macular fibrosis in type 3 macular neovascularisation.

AIMS: To explore prognostic multimarker models for progression to macular fibrosis (MF) over 24 months specific to type 3 macular neovascularisation (T3 MNV). METHODS: This retrospective, exploratory, single-centre, cohort study comprised 65 eyes of 43 Caucasian patients with treatment naive T3 MNV, all with a 24-month follow-up post anti-VEGF therapy using a strict pro-re-nata (PRN) regimen. Data on demographic features, clinical findings, frequency of intravitreal treatments and optical coherence tomography biomarkers were collected at baseline and after 12 and 24 months of follow-up. Logistic regression models (LRM) and receiver-operating curve (C-index) analyses were performed to evaluate the prognostic ability of the studied biomarkers in discriminating between MF affected and unaffected patients. RESULTS: At final follow-up, MF was present in 46.2% of eyes. Subretinal hyper-reflective material (SHRM) and subretinal pigment epithelium multilaminar hyper-reflectivity (multilaminae) emerged as significant predictors for MF, with adjusted odds ratios (OR) of 18.0 (95% CL 13.4 to 24.1) and 11.8 (95% CL 8.66 to 16.0), respectively. Additionally, the presence of multifocal lesions (OR 0.04, 95% CL 0.01 to 0.30) appeared to decrease the likelihood of MF. C-indexes for the selected LRMs ranged between 0.92 and 0.88, indicating a comparably high discriminant ability. Despite consistent treatment schedules between the two groups (MF: median intravitreal treatment (IVT) number=10.5, IQR=7; non-MF: median IVT=10, IQR=6), a decline in best-corrected visual acuity was noted in the group with MF onset over the 24-month follow-up (-13.0 ETDRS letters; 95% CL -22.1 to -3.9; p=0.006). CONCLUSION: Our study identifies SHRM and multilaminae as relevant predictors of 24-month onset of MF in patients with T3 MNV. These findings enrich our understanding of the development of MF in T3 MNV and can guide improved risk prognostication. Future research should consider larger samples and prospective designs to validate these predictors.

Ocular surface in posterior segment surgery.

Nowadays, the technological breakthroughs of mini-invasive vitreo-retinal surgery improved the perioperative management and the outcomes of millions of patients. The most common procedures include pars plana vitrectomy, episcleral surgery, intravitreal injections, and laser photocoagulation. Potential sight and non-sight-threatening side effects have been reported during the follow-up period. Ocular surface disbalance can be induced by the aforementioned procedures, resulting in mild to severe ocular discomfort symptoms. This condition may recognize different causes such as pre-existing or concomitant diseases of the external eye, the surgical procedure damage of the anatomical or physiological structures of the ocular surface, the prolonged side effects induced by the chronic topical treatment that may be toxic to the external eye.In addition to the most frequent dry eye-related signs and symptoms, subconjunctival haemorrhages, corneal epithelium damage, partial loss of corneal sensitivity or changes in corneal nerve density could postoperatively affect our patients.In conclusion, any surgical trauma directed to the posterior segment of the eye may cause the loss of the ocular surface homeostasis. Ophthalmologists should not only recognise and treat, but possibly prevent, all patients' symptoms that could manifest in the postoperative time.

Multimodal imaging for the management of Lyme-associated uveitis: A case report from an Italian tertiary center.

INTRODUCTION: Lyme borreliosis may present with different systemic manifestations and also the ocular involvement may be difficult to diagnose because of its multifaceted presentation. Considering the growing incidence of Lyme disease in European countries, ophthalmologist should be trained to distinguish ocular borreliosis. CASE REPORT: Several clinical presentations have been previously described, including uveitis, unilateral or bilateral chorioretinitis, keratitis, episcleritis, papillitis and ischemic optic neuropathy, retinal vasculitis and acute posterior multifocal placoid pigment epitheliopathy (APMPPE); however our case report showed a rare presentation with the presence of unilateral uveitis with vitreitis and multiple, patchy, yellowish lesions, in association with retinal vasculitis. This clinical picture was to be considered in differential diagnosis with ocular Toxoplasmosis. CONCLUSIONS: The appropriate management of this patient was made possible by the combination of multimodal imaging and appropriate laboratory tests, representing the optimal process in the diagnostic and therapeutic pathway in high-risk patients for ocular Lyme disease.

The multifaceted presentation of syphilitic chorioretinitis examined by multimodal imaging: A case series.

Ocular syphilis is also known as the 'great masquerader' for the wide variety of clinical features associated with this infection. Although chorioretinitis represents the most frequent manifestation in the posterior pole, other clinical entities can be described, including retinal vasculitis, optic disc disorders, necrotizing vasculitis and acute syphilitic posterior placoid chorioretinopathy (ASPPC).This latter is an infrequent ocular manifestation of syphilis, whose pathophysiology remains still unknown; however, multimodal imaging, including optical coherence tomography angiography (OCTA), has enabled us to better describe its pathophysiology and clinical course.In this study we report a case series of 3 different patients with syphilis-related chorioretinopathies; in this regard, the role of multimodal imaging has emerged has an extremely useful approach in order to better understand the pathophysiology of syphilitic chorioretinopathies. This could help clinicians (both ophthalmologist and infectious disease specialists) to early treat and prevent the severe ocular complications related to this fearsome disease.

Choroidal changes in intermediate age-related macular degeneration patients with drusen or pseudodrusen.

Reticular pseudodrusen are associated with a thinner choroid. The aim of our study was to determine the differences in central choroidal thickness and choriocapillaris vascular flow area between eyes with and without reticular pseudodrusen using swept-source optical coherence tomography and swept-source optical coherence tomography angiography. We conducted a retrospective case control study which included 27 eyes from 27 consecutive patients with intermediate age-related macular degeneration and 17 eyes from 17 healthy participants. Complete ophthalmic examinations were carried out including axial length measurements; fundus color retinography; fundus autofluorescence; swept-source optical coherence tomography and swept-source optical coherence tomography angiography; central choroidal thickness and choriocapillaris vascular flow area. Patients were classified as no reticular pseudodrusen, mild reticular pseudodrusen, and severe reticular pseudodrusen. Mean central choroidal thickness in patients exhibiting severe reticular pseudodrusen (110 ± 56 µm) was significantly smaller than in patients with no reticular pseudodrusen (201 ± 76 µm, p < 0.01). Mean choriocapillaris vascular flow area in severe reticular pseudodrusen patients (45.2% ± 3.0%) was also significantly less than in patients with no (47.9% ± 1.6%, p < 0.001) and mild reticular pseudodrusen (47.7% ± 1.0%, p < 0.05). Stepwise multiple regression models confirmed the association of reticular pseudodrusen with central choroidal thickness (p < 0.001) and choriocapillaris vascular flow area (p < 0.01) even after accounting for age, axial length, and refractive error. Soft drusen were not associated with changes in either central choroidal thickness (p = 0.13) nor choriocapillaris vascular flow area (p = 0.29). A significant, positive relationship was found between central choroidal thickness and choriocapillaris vascular flow area (r = 0.44, p = 0.01). Therefore, both central choroidal thickness and choriocapillaris vascular flow area are decreased in eyes with reticular pseudodrusen, as compared to healthy eyes and intermediate age-related macular degeneration eyes not exhibiting reticular pseudodrusen. In addition, central choroidal thickness and choriocapillaris vascular flow area are related, and the reduction of either is directly associated to the severity of reticular pseudodrusen. Further studies are needed to assess the clinical significance of these findings.

Real-Life Management of Patients with Retinal Vein Occlusion Using I-Macula Web Platform.

AIM: Real-life evaluation in the management of patients affected by macular edema secondary to retinal vein occlusion. MATERIAL AND METHODS: A retrospective, observational study using the I-Macula Web platform. RESULTS: Thirty-five patients (37 eyes; 15 females and 20 male) affected by RVO were analysed. At 12 months, there was a statistically significant improvement of best-corrected visual acuity (p = 0.0235) and central macular thickness (p < 0.0001). The mean change in visual acuity was 8.9 letters. Twenty-seven eyes underwent DEX implant (n = 62; mean: 2.29) only. Of these, 8, 4, 14, and 1 eyes underwent 1, 2, 3, and 4 DEX implants, respectively. The remaining 10 eyes were also injected with ranibizumab (n = 49; mean: 4.9). At 12 months, 12 eyes (32.5%) presented a dry macula, whereas the remaining 25 eyes (67.5%) still had macular edema. Mean interval between the first and second treatment (T1) and between the second and third treatment (T2) were 5.15 and (T2) 3.7 months, respectively. Where only DEX implants were received, T1 and T2 was 5.1 and 4.9 months, respectively. CONCLUSIONS: This study confirms that DEX implants and/or anti-VEGF drugs improve visual acuity and central macular thickness in patients affected by RVO.

Choroidal Vascular Flow Area in Central Serous Chorioretinopathy Using Swept-Source Optical Coherence Tomography Angiography.

Purpose: To report the choroidal vascular flow area in eyes with central serous chorioretinopathy (CSC) compared with healthy subjects and unaffected fellow eyes using swept-source (SS) optical coherence tomography (OCT) angiography. Methods: Prospective case series of 19 eyes of 19 consecutive patients affected by CSC, compared with 15 unaffected fellow eyes and 20 eyes of 10 healthy subjects. Patients underwent SS-OCT angiography in order to evaluate the choroidal vascular flow area of choriocapillaris (CC) and deeper choroidal layers. Results: The choroidal vascular flow area was higher in eyes with CSC than in control eyes (53.4 ± 5.8% vs. 49.45 ± 8.16%; P = 0.0001). Within the choroid of CSC patients choroidal vascular flow area of the CC was significantly lower than the deeper level (50.97 ± 2.8% vs. 54.22 ± 6.3%; P = 0.025). There were no differences within the choroid of control eyes. The choroidal vascular flow area at the level of the CC was higher in the unaffected fellow eye (50.74 ± 0.9%; P = 0.019) than in control eyes. Choroidal vascular flow area of unaffected fellow eyes did not differ from CSC eyes (P = 0.17). The choroidal vascular flow area at the level of the CC was higher in the CSC eyes (P = 0.0009) compared with unaffected fellow eyes. Conclusions: Choroidal vascular flow area is larger in CSC eyes compared with control eyes. However, within the choroid of eyes with CSC, there might be some differences in flow area between CC and deeper choroidal levels. This difference might be secondary to a compensatory mechanism of the choroid.

I-Maculaweb: A Tool to Support Data Reuse in Ophthalmology.

This paper intends to present a Web-based application to collect and manage clinical data and clinical trials together in a unique tool. I-maculaweb is a user-friendly Web-application designed to manage, share, and analyze clinical data from patients affected by degenerative and vascular diseases of the macula. The unique and innovative scientific and technological elements of this project are the integration with individual and population data, relevant for degenerative and vascular diseases of the macula. Clinical records can also be extracted for statistical purposes and used for clinical decision support systems. I-maculaweb is based on an existing multilevel and multiscale data management model, which includes general principles that are suitable for several different clinical domains. The database structure has been specifically built to respect laterality, a key aspect in ophthalmology. Users can add and manage patient records, follow-up visits, treatment, diagnoses, and clinical history. There are two different modalities to extract records: one for the patient's own center, in which personal details are shown and the other for statistical purposes, where all center's anonymized data are visible. The Web-platform allows effective management, sharing, and reuse of information within primary care and clinical research. Clear and precise clinical data will improve understanding of real-life management of degenerative and vascular diseases of the macula as well as increasing precise epidemiologic and statistical data. Furthermore, this Web-based application can be easily employed as an electronic clinical research file in clinical studies.

Early Swept-Source Optical Coherence Tomography Angiography Findings in Unilateral Acute Idiopathic Maculopathy.

Unilateral acute idiopathic maculopathy (UAIM) is a rare disorder presenting in young people with an acute onset of unilateral central visual loss often associated with a prodromal flu-like illness. The authors present the early anatomical findings of a 35-year-old man clinically diagnosed with UAIM using swept-source optical coherence tomography (SS-OCT) and SS-OCT angiography.

Efficacy of botulinum toxin type A treatment of functional impairment of degenerative hip joint: Preliminary results.

OBJECTIVE: The aim of this study was to investigate the effect of botulinum toxin type A injection into the adductor muscles in reducing pain and improving joint mobility and quality of life in patients affected by hip osteoarthritis. METHODS: A total of 39 outpatients, mean age 68 years (age range 41-82 years), were evaluated using the Harris Hip Score to test hip function, a visual analogue scale to measure pain intensity and the Short Form 36 (SF-36) questionnaire to assess patient well-being and quality of life at baseline, 2, 4 and 12 weeks after treatment with botulinum toxin type A. A total of 400 U of botulinum toxin type A (Dysport) was injected into the adductor longus muscle and the adductor magnus muscle. RESULTS: The Harris Hip Score increased significantly after 2, 4 and 12 weeks (df 3, chi2 = 45.1; p < 0.0001). A significant decrease in pain intensity was detected at all the follow-up visits, after 2, 4 and 12 weeks (df 3; chi2 = 27.8; p < 0.001). The SF-36 score was significantly higher 4 and 12 weeks after treatment. At each evaluation visit a significant correlation was detected between decreased pain and improved hip mobility. CONCLUSION: Botulinum toxin type A induced a reduction in pain, indicating that this might be an innovative, less invasive treatment in patients affected by severe hip osteoarthritis, with remarkable effects on the clinical management of this disease.

Preoperative autologous blood donation in primary total knee arthroplasty: critical review of current indications.

Preoperative autologous blood donation (PABD) is a well established transfusion practice in elective orthopaedic surgery, involving immunologic and infective advantages but also involving exposure to not negligible risks, and costs as well. The aim of this study was to assess the real need for blood transfusions in primary total knee arthroplasty (TKA). Between January 2000 and July 2005, 214 patients underwent primary unilateral TKA. Altogether, 416 autologous blood units were collected, however only 47 (11.3%) were transfused. Thirty-eight patients (17.8%) received autologous blood, while 4 of them (10.5%) also received allogeneic blood. Based on the results of this study, PABD should be recommended in well selected patients undergoing TKA: older female patients with a low basal haemoglobin level.

Effect of cold-induced hyperthyroidism on H2O2 production and susceptibility to stress conditions of rat liver mitochondria.

Previous studies have shown that T3 treatment and cold exposure induce similar biochemical changes predisposing rat liver to oxidative stress. This suggests that the liver oxidative damage observed in experimental and functional hyperthyroidism is mediated by thyroid hormone. To support this hypothesis we investigated whether middle-term cold exposure (2 and 10 days), like T3 treatment, also increases H2O2 release by liver mitochondria. We found that the rate of H2O2 release increased only during State 4 respiration, but faster flow of reactive oxygen species (ROS) from mitochondria to the cytosolic compartment was ensured by the concomitant increase in tissue mitochondrial proteins. Cold exposure also increased the capacity of mitochondria to remove H2O2. This indicates that cold causes accelerated H2O2 production, which might depend on enhanced autoxidizable carrier content and should lead to increased mitochondrial damage. Accordingly, mitochondrial levels of hydroperoxides and protein-bound carbonyls were higher after cold exposure. Levels of low-molecular weight antioxidants were not related to the extent of oxidative damage, but susceptibility to both in vitro oxidative challenge and Ca2+-induced swelling increased in mitochondria from cold exposed rats. The cold-induced changes in several parameters, including susceptibility to swelling, were time dependent, because they were apparent or greater after 10 days cold exposure. The cold-induced increase in swelling may be a feedback mechanism to limit tissue oxidative stress, purifying the mitochondrial population from ROS-overproducing mitochondria, and the time course for such change is consistent with the gradual development of cold adaptation.

Effect of thyroid state on susceptibility to oxidants and swelling of mitochondria from rat tissues.

The effects of the thyroid state on oxidative damage, antioxidant capacity, susceptibility to in vitro oxidative stress and Ca(2+)-induced permeabilization of mitochondria from rat tissues (liver, heart, and gastrocnemious muscle) were examined. Hypothyroidism was induced by administering methimazole in drinking water for 15 d. Hyperthyroidism was elicited by a 10 d treatment of hypothyroid rats with triiodothyronine (10 micro g/100 g body weight). Mitochondrial levels of hydroperoxides and protein-bound carbonyls significantly decreased in hypothyroid tissues and were reported above euthroid values in hypothyroid rats after T(3) treatment. Mitochondrial vitamin E levels were not affected by changes of animal thyroid state. Mitochondrial Coenzyme Q9 levels decreased in liver and heart from hypothyroid rats and increased in all hyperthyroid tissues, while Coenzyme Q10 levels decreased in hypothyroid liver and increased in all hyperthyroid tissues. The antioxidant capacity of mitochondria was not significantly different in hypothyroid and euthyroid tissues, whereas it decreased in the hyperthyroid ones. Susceptibility to in vitro oxidative challenge decreased in mitochondria from hypothyroid tissues and increased in mitochondria from hyperthyroid tissues, while susceptibility to Ca(2+)-induced swelling decreased only in hypothyroid liver mitochondria and increased in mitochondria from all hyperthyroid tissues. The tissue-dependence of the mitochondrial susceptibility to stressful conditions in altered thyroid states can be explained by different thyroid hormone-induced changes in mitochondrial ROS production and relative amounts of mitochondrial hemoproteins and antioxidants. We suggest that susceptibilities to oxidants and Ca(2+)-induced swelling may have important implications for the thyroid hormone regulation of the turnover of proteins and whole mitochondria, respectively.

Effect of thyroid state on H2O2 production by rat liver mitochondria.

It has been suggested that activation of mitochondrial respiration by thyroid hormone results in oxidative tissue injury secondary to increased reactive oxygen species production. In order to throw light on this subject, the effects of thyroid state on O2 consumption and H2O2 release by rat liver mitochondria were investigated. Hypothyroidism decreased the rates of O2 consumption and H2O2 release by succinate or pyruvate/malate-supplemented mitochondria during both State 4 and State 3 respiration, whereas hyperthyroidism increased such rates. Conversely, with both substrates and during either respiration phase, the percentage of O2 released as H2O2 was not significantly affected by thyroid state. On the other hand, the capacity of mitochondria to remove H2O2 increased by about 17% in hyperthyroid rats and decreased by about 35% in hypothyroid ones. This result indicates that the ratio between H2O2 production and release and so the percentage of O2 turned into H2O2 instead of being reduced to water increase in the transition from hypothyroid to hyperthyroid state. In light of previous observations that mitochondrial content of cytochromes and ubiquinone also increases in such a transition, the modifications of H2O2 production appear to be due to a modulation by thyroid hormone of the mitochondrial content of the autoxidisable electron carriers. This view is supported by measurements of H2O2 release in the presence of respiratory inhibitors, which show that the thyroid state-linked changes in H2O2 production occur at H2O2 generator sites of both Complex I and Complex III.