What to expect from primary inferior oblique overaction after esotropia surgery : Primary inferior oblique overaction in esotropia.

BACKGROUND: Overelevation in adduction is common in patients with primary esotropia. This study evaluates the variation in ocular motility pattern in patients with primary inferior oblique (IO) muscle overaction after esotropia surgery. METHODS: The medical records of consecutive patients who underwent surgery for infantile, partially accommodative, and basic esotropia over eleven years and had at least one year of follow-up were reviewed. Patients with primary inferior oblique muscle overaction (IOOA) presented at baseline or during follow-up were selected and divided according to the first surgery performed concurrently with horizontal rectus surgery: without IO recession (NO-recess), with unilateral IO recession (UNIL-recess), and with bilateral IO recession (BIL-recess). The success (version normalisation or at least 2 points upgrade in severity scale [0-4] in the operated eye), recurrence rates, and the evolution of the non-operated IO muscles were evaluated. RESULTS: One hundred and ten patients were included - 53 NO-recess, 26 UNIL-recess, and 31 BIL-recess. Medial rectus muscle posterior fixation sutures surgery (PFS) was performed in 88.2% of patients for esotropia. A recession with graded anterior transposition was the weakening IO procedure. In the NO-recess group, 28 (52.8%) patients normalised their mild IOOA after PFS surgery alone. In the UNI-recess group, the success rate was 88.5%, with 16 (61.5%) patients showing worsened IO muscle of the fellow eye, which prompted additional surgery in 10 patients. In the BIL-recess group, all 31 patients improved the adduction pattern of the operated eye for an 80.6% success rate (6 improved marginally). CONCLUSION: Graded anterior transposition of the inferior oblique muscle effectively normalises versions. However, it's frequent for a contralateral overaction to become manifest after unilateral IO surgery.

Retinal and choroidal vasoreactivity in central serous chorioretinopathy.

PURPOSE: This study aims to investigate retinal and choroidal vascular reactivity to carbogen in central serous chorioretinopathy (CSC) patients. METHODS: An experimental pilot study including 68 eyes from 20 CSC patients and 14 age and sex-matched controls was performed. The participants inhaled carbogen (5% CO2 + 95% O2) for 2 min through a high-concentration disposable mask. A 30° disc-centered fundus imaging using infra-red (IR) and macular spectral domain optical coherence tomography (SD-OCT) using the enhanced depth imaging (EDI) technique was performed, both at baseline and after a 2-min gas exposure. A parametric model fitting-based approach for automatic retinal blood vessel caliber estimation was used to assess the mean variation in both arterial and venous vasculature. Choroidal thickness was measured in two different ways: the subfoveal choroidal thickness (SFCT) was calculated using a manual caliper and the mean central choroidal thickness (MCCT) was assessed using an automatic software. RESULTS: No significant differences were detected in baseline hemodynamic parameters between both groups. A significant positive correlation was found between the participants' age and arterial diameter variation (p < 0.001, r = 0.447), meaning that younger participants presented a more vasoconstrictive response (negative variation) than older ones. No significant differences were detected in the vasoreactive response between CSC and controls for both arterial and venous vessels (p = 0.63 and p = 0.85, respectively). Although the vascular reactivity was not related to the activity of CSC, it was related to the time of disease, for both the arterial (p = 0.02, r = 0.381) and venous (p = 0.001, r = 0.530) beds. SFCT and MCCT were highly correlated (r = 0.830, p < 0.001). Both SFCT and MCCT significantly increased in CSC patients (p < 0.001 and p < 0.001) but not in controls (p = 0.059 and 0.247). A significant negative correlation between CSC patients' age and MCCT variation (r = - 0.340, p = 0.049) was detected. In CSC patients, the choroidal thickness variation was not related to the activity state, time of disease, or previous photodynamic treatment. CONCLUSION: Vasoreactivity to carbogen was similar in the retinal vessels but significantly higher in the choroidal vessels of CSC patients when compared to controls, strengthening the hypothesis of a choroidal regulation dysfunction in this pathology.

Prevalence and Area of Retinal Pigment Epithelium and Outer Retinal Atrophy in Eyes with Non-Exudative Macular Neovascularization.

PURPOSE: The objective of this study wasto assess the prevalence of complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) in patients with unilateral exudative age-related macular degeneration (AMD) of the fellow eye and establish if the presence of non-exudative macular neovascularization (NE-MNV) influences the prevalence of RPE and outer retinal atrophy in eyes with AMD. METHODS: This is an observational cross-sectional study of 68 patients with unilateral exudative AMD. Demographic and clinical data were collected, and multimodal retinal imaging was performed in all patients. Two groups of patients were defined according to the presence (NE-MNV) or absence (no NE-MNV) of NE-MNV in the study eye. We compared the prevalence of tomographic cRORA and fundus autofluorescence (FAF) geographic atrophy (GA) and differences in cRORA greatest linear diameter (GLD) and GA area between groups. RESULTS: Globally, cRORA was present in 11 eyes (16.2%), FAF GA was present in 10 eyes (14.7%), and NE-MNV was present in 10 eyes (14.7%) of patients with unilateral exudative AMD of the fellow eye. The overall cRORA GLD was 1,950.64 ± 1,428.31 µm, and the mean area of GA was 9.25 ± 7.50 mm2. Regarding comparisons between groups, cRORA was present in 9 eyes (15.5%) without NE-MNV and in 2 eyes (20%) with NE-MNV (p = 0.66). Tomographic signs of atrophy were more frequent in eyes with NE-MNV (50% vs. 24.1% in eyes without NE-MNV; p = 0.008). No significant differences were found in cRORA GLD (p = 0.30) between groups. Eyes with NE-MNV and eyes without NE-MNV had a similar prevalence of FAF GA (2 eyes out of 10 and 8 eyes out of 58, respectively; p = 0.64). Eyes with NE-MNV had a smaller mean area of GA (2.07 ± 0.24 mm2 vs. 11.05 ± 7.34 mm2; p = 0.01). CONCLUSION: In our study, the presence of NE-MNV was not associated with the prevalence of cRORA and/or FAF GA. Nonetheless, eyes with NE-MNV presented smaller areas of GA, which suggests that this type of neovascularization may prevent the progression of RPE and outer retinal atrophy. Longitudinal studies are required to confirm these preliminary results.

Quantitative Optical Coherence Tomography Angiography Biomarkers for Alport Syndrome.

PURPOSE: The aim of this study was to evaluate microvascular abnormalities of patients with Alport syndrome (AS) using optical coherence tomography angiography (OCT-A) quantitative biomarkers. METHODS: This was cross sectional, prospective evaluation of consecutive patients with AS and healthy subjects. AS diagnosis was performed by the genetic test. All participants underwent a retinal vasculature evaluation by spectral-domain optical coherence tomography (SD-OCT) and OCT-A of the macula. Quantitative analysis included whole vascular density, foveal avascular zone area, fractal dimension (FD), and lacunarity (LAC). RESULTS: Ninety-four eyes were included in this study, 45 eyes from patients with AS and 49 eyes from healthy subjects. The pathogenic mutation in the COL4A5 gene on the chromosome X was found in 14 patients; the pathogenic autosomal recessive mutations in the COL4A3 gene were found in 9 patients. Quantitative evaluation demonstrated a significant difference between AS and healthy subjects on LAC of the superficial capillary plexus and deep capillary plexus (DCP) (p < 0.001 and p < 0.001, respectively) and on FD in the DCP (p < 0.001). CONCLUSION: The DCP Alport patients have a higher vessel nonuniformity than DCP of healthy subjects. We hypothesize that endothelial cell lesion in the setting of low resistance at the DCP circuit could lead to long-term structural disorganization.

Cerebral Neurovascular Coupling Impairment in Central Serous Chorioretinopathy.

BACKGROUND: Central serous chorioretinopathy (CSCR) is a chorioretinal disorder resulting from choroidal hyperpermeability. Its comorbidities as hypertension, coronary disease, and psychological stress, suggest that it might reflect a more generalized vascular dysfunction. OBJECTIVES: The aim of the study was to assess the cerebrovascular regulation integrity, using cerebral autoregulation (CA), carbon dioxide vasoreactivity (VR), and neurovascular coupling (NVC) in CSCR. METHODS: This observational pilot study included 20 CSCR patients and 14 age- and sex-matched controls. A State-Trait Anxiety Inventory (STAI) inquiry was full-filled. Continuous measurement of cerebral blood flow velocity (CBFV), arterial blood pressure, heart rate, and end-tidal carbon dioxide was performed. VR was assessed during hypercapnia (inhaling carbogen gas) and hypnocapnia (hyperventilation). For NVC, the CBFV relative increase during mental activation using the N-Back Task was calculated. RESULTS: No significant differences in systemic hemodynamic parameters, CA or VR, were found between both groups. During the NVC performance, the average CBFV rise during mental stress was significantly lower in CSCR (p = 0.011). A significant negative correlation was found between STAI scores and NVC. CONCLUSIONS: CSCR patients presented a significantly impaired cerebral NVC compared to controls, supporting the theory of a potential systemic vascular dysfunction. Stress could be related to this NVC impairment.

Correlation Between Ophthalmologic and Neuroradiologic Findings in Type 1 Neurofibromatosis.

BACKGROUND: Neurofibromatosis Type 1 (NF-1) is a genetic disease affecting the eye, and ocular findings such as Lisch nodules (LN) or optic pathway gliomas (OPGs) are a part of its diagnostic criteria. Recent imaging technologies such as infrared (IR) imaging and optical coherence tomography (OCT) have highlighted the visualization of choroidal focal abnormalities in these patients, even in the absence of other ocular lesions. This study aimed to establish a morphological multimodal evaluation of choroidal findings in patients with NF-1, correlating them with central nervous system (CNS) findings. METHODS: This retrospective study included 44 eyes from 22 patients with NF-1. Central 30° IR imaging was obtained, and the number and total area of detectable lesions were calculated. Both macular and optic disc scanning with OCT were performed, with and without the enhanced depth imaging technique, to assess the presence of choroidal focal hyperreflective lesions. Central macular thickness, ganglion cell layer, and outer nuclear layer thickness were assessed, as well as subfoveal choroidal thickness. The peripapillary retinal nerve fiber layer (RNFL) thickness was also assessed. Patients' magnetic resonance images (MRI) were reviewed and categorized by a neuroradiology specialist, determining the presence of OPGs and CNS hamartomas. Correlations between the ophthalmological and neuroradiological findings were established. RESULTS: Patients' mean age was 16.4 ± 7.3 years and 59.1% were women. On the MRI, 86.4% of the patients had CNS hamartomas, and 34.1% of the eyes had OPGs. LN were described in 29.5% of the eyes, whereas a total of 63.4% of the eyes presented the characteristic hyperreflective lesions in IR imaging, all of them matching the underlying choroidal lesions. A mean of 2.9 ± 3.3 lesions per eye and a median total lesion area of 1.52 mm2 were found. The presence of OPGs was correlated with a greater number (P = 0.004) and a larger area (P = 0.006) of IR lesions. For a cut-off of 3.5 lesions per eye, the sensitivity and specificity for the presence of OPGs were 75% and 80%, respectively. For a total lesion area of 2.77 mm2, the sensitivity and specificity for the presence of OPGs were 69.2% and 93.1%, respectively. Eyes with OPGs presented a significant reduction in the temporal RNFL (P = 0.018) thickness, as well as a reduction in subfoveal choroid thickness (P = 0.04). No relations were found between CNS hamartomas and ophthalmological findings. CONCLUSIONS: This study suggests that focal choroidal abnormalities are correlated with the presence of CNS lesions as OPGs in patients with NF-1, and it might be a surrogate for the need for CNS imaging in these patients.

Child with a mild phenotype of Incontinentia Pigmenti and inner retinal dysfunction.

PURPOSE: To describe a case of a child with mild phenotype of Incontinentia Pigmenti (IP), with changes in Spectral-Domain Optical Coherence Tomography (SD-OCT) and Optical Coherence Tomography Angiography (OCT-A) and an electronegative dark-adapted (DA) 3.0 electroretinogram (ERG), suggestive of inner retinal dysfunction. CASE REPORT: We described a 7-year-old female child with IP. Her best corrected acuity was 8/10 in the right eye and 6/10 in the left eye. Biomicroscopy, intraocular pressure and fundoscopy were normal. The electroretinography findings showed an electronegative DA 3.0 ERG with a normal a-wave but a b-wave that did not elevate above baseline. SD-OCT identified irregularities in the outer plexiform layer in both eyes, and OCT-A assessment revealed at the superficial capillary plexus, areas of decrease in the flow in parafoveal and perifoveal regions. CONCLUSION: Classically, IP affects the peripheral retina; however, vascular and structural changes in macula can occur as well. To our knowledge, we report the first electronegative electroretinogram in a patient with IP.

Long-term progression of geographic atrophy in age-related macular degeneration does the phakic status matter?

PURPOSE: To assess the long-term risk of geographic atrophy (GA) progression after cataract surgery. METHODS: Subjects with GA secondary to AMD followed for at least 1 year with fundus autofluorescence imaging and with at least two visits at our centre were included. Patients with wet AMD, disciform scar, past history of intravitreal injections or laser treatment, other maculopathies and with poor quality images were excluded. GA area at baseline and at follow-up visit was measured. Three study groups were defined according to their phakic status: (A) pseudophakia, (B) phakic and (C) phacoemulsification surgery performed during the study. Differences of GA area progression were compared between these study groups. In addition, comparison between GA progression rate in group (C) before and after the surgery was performed. The enlargement rate (ER) was calculated for lesion size after transforming the measurements to the square-root scale. RESULTS: A total of 92 eyes of 92 patients were enrolled. Median follow-up time was 4 [1-10] years. Regarding the eye's phakic status, 29 (31.5%) were pseudophakic and 63 (68.5%) were phakic; of these, 22 underwent phacoemulsification during the study. Overall, the median baseline and follow-up area of GA were 1.42 [0.04-32.10] mm2 and 6.48 [0.25-47.40] mm2, respectively. The ER was similar between phakic and pseudophakic eyes (0.18 [0.01-1.03] vs 0.15 [0.01-0.65] mm/year, p = 0.62). In patients that underwent cataract surgery during the study, the GA ER remained stable (0.13 [0.01-0.92] vs 0.14 [0.01-0.63] mm/year, p = 0.43). CONCLUSION: These results suggest that cataract surgery does not increase the risk of pre-existing GA progression. Therefore, cataract surgery seems safe and a potential therapeutic weapon to improve visual acuity and consequently quality of life in GA patients.

Predicting retinal pigment epithelium remodelling and its functional impact.

PURPOSE: To identify predictive factors for RPE tear remodelling and its correlation with functional and morphological outcomes. METHODS: Retrospective longitudinal study of patients with retinal pigment epithelium (RPE) tears secondary to age-related macular degeneration (AMD). Imaging was performed using spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF). RPE layer integrity in the RPE-denuded area was examined with SD-OCT, and variation in the RPE-denuded homogeneous hypofluorescent area was examined with FAF over time for each case (eye). Patients were divided in two groups, according to the presence (Rem) or absence (No Rem) of evidence of RPE tear remodelling. Data were collected at three different time points: at baseline (at diagnosis of exudative AMD), at RPE tear diagnosis, and at the last available follow-up. Using SD-OCT, the following parameters were evaluated: type of CNV, type of PED and its dimensions, presence of subretinal (SRF) or intraretinal (IRF) fluid, central retinal thickness (CRT), presence and location of hyperreflective dots, and dimension and location of RPE tear. RESULTS: This study included 32 eyes from 31 patients (19 female and 12 male), with RPE tears secondary to AMD. RPE remodelling after tear development was evident in 17 (53.1%) eyes after 7 [1-59] months. Anatomical recovery was associated with a younger age at RPE tear diagnosis (73 ± 7 vs. 81 ± 7 years old, p=0.01), smaller and narrower retinal pigment epithelial detachment (PED) at tear diagnosis (height 369 vs. 602 µm, p=0.02; width 2379 vs. 3378 µm, p=0.04), and the presence of SRF at tear diagnosis (94% vs. 53%, p=0.02). After adjusting for other covariates, a younger age at RPE tear diagnosis maintained significant association with RPE tear remodelling. RPE tear remodelling did not correlate with a better visual outcome at last follow-up (43 ± 22.8 vs. 34 ± 23.8 ETDRS letters, p=0.30). Final VA was directly proportional to VA at tear diagnosis (r= 0.654; p<0.001) and correlated negatively with PED width at tear diagnosis (r = -0.388; p=0.03). CONCLUSION: RPE remodelling was evident in half of our sample and was associated with a younger age, smaller and narrower PED at RPE tear diagnosis, and presence of SRF also at tear diagnosis. Nevertheless, this structural recovery did not result in a better functional outcome.

Longitudinal Retinal Changes Induced by Hydroxychloroquine in Eyes without Retinal Toxicity.

INTRODUCTION: This study aimed to evaluate the longitudinal changes in retinal layer thickness in patients treated with hydroxychloroquine without retinal toxicity. METHODS: This is a longitudinal retrospective study of patients taking hydroxychloroquine followed in a hydroxychloroquine retinal toxicity screening program of a tertiary hospital between January 2010 and April 2019. Patients who performed 2 optical coherence tomography (OCT) scans at least 1 year apart were included. All subjects with hydroxychloroquine suspected or confirmed retinal toxicity, glaucoma, retinal pathology, or poor segmented images were excluded. Spectral-domain optical coherence tomography (Spectralis HRA-OCT, Heidelberg) was used to evaluate the macular area. Automatically segmented ETDRS retinal thickness maps were compared between the first and the last OCT evaluation available. Full retina (FR), inner retina (IRL), ganglion cells (GCL), inner nuclear (INL), and outer retina (ORL) layer thicknesses were measured in the foveolar, paracentral, and peripheral area. RESULTS: The population included 144 eyes of 144 patients. The mean interval between OCT scans was 38.1 ± 18.4 months, and the mean cumulative dose was 406.9 ± 223.9 g. Foveolar (p = 0.040, p = 0.006, and p = 0.001, respectively) and paracentral (p = 0.006, p = 0.001, and p = 0.005, respectively) FR, IRL, and GCL decreased overtime. No differences were found in INL or ORL. A very weak correlation was found between age and foveal IRL change overtime (p = 0.037; R = 0.175), as well as between the hydroxychloroquine time of use and foveal GCL variation (p = 0.032; R = 0.179). CONCLUSION: Hydroxychloroquine was found to cause progressive thinning of the inner retinal layers, specifically in the GCL of the foveolar and paracentral areas, but no changes were observed in the outer retina.

Cytokines and Growth Factors as Predictors of Response to Medical Treatment in Diabetic Macular Edema.

Diabetic macular edema (DME) is the most common cause of visual loss in patients with diabetes. Antivascular endothelial growth factors (anti-VEGF) agents are first-line therapy for DME. Nevertheless, up to 60% of patients (depending on the anti-VEGF drug used) have an inadequate response to anti-VEGF treatment. Several cytokines are increased in aqueous humor of patients with DME. Differences in response to treatment may be related to baseline cytokine levels. Intravitreal corticosteroids may be used as an alternative to anti-VEGF agents. Steroids have a different pharmacological profile and act on different pathophysiologic mechanisms. Their effect on aqueous humor cytokines is different from the effect of anti-VEGF therapy. This review highlights the major cytokines involved in DME and evaluates whether baseline cytokine levels could be predictors of response to treatment in DME. SIGNIFICANCE STATEMENT: Antivascular endothelial growth factor (anti-VEGF) agents are efficient as diabetic macular edema (DME) treatment. However, in some cases, DME fails to respond to anti-VEGF intravitreal injections. Changes in cytokine levels after treatment supported the idea that other cytokines than VEGF are implicated in DME pathogenesis and could be predictors of response to anti-VEGF treatment or corticosteroids allowing targeted and individualized therapy guided by cytokine levels.

Clinical Characteristics of the Charles Bonnet Syndrome in Patients with Neovascular Age-Related Macular Degeneration: The Importance of Early Detection.

PURPOSE: We investigated the characteristics, prognosis, and clinical outcome of the Charles Bonnet syndrome (CBS) in patients with neovascular age-related macular degeneration (AMD). METHODS: Five hundred psychiatrically healthy patients with neovascular AMD were screened for CBS. The individuals that fulfilled the inclusion criteria were systematically interviewed using a structured questionnaire that covered the impact, prognosis, risk factors, phenomenology, symptoms, and knowledge about the syndrome. A control group of 45 patients was used for comparison. Demographic data, current medication, and ocular risk factors were collected in all patients. RESULTS: Forty-five patients with CBS were identified. The majority of patients reported images that consisted of colored (62%) animals (44%) or faces (42%) that lasted for seconds (53%). Most patients reported a self-limited disease with a median duration of symptoms between 9 and 11.5 months, with only 7% knowing about CBS at symptom onset. The degree of visual deficit did not predict the characteristics, complexity, frequency, duration, or impact of visual hallucinations. One-third of patients reported negative outcome, which was associated with shorter duration of CBS (p = 0.023), fear-inducing images (p < 0.001), and impact on daily activities (p = 0.015). CONCLUSION: The prevalence of CBS in neovascular AMD patients is high and clinically relevant. Patients with recent onset of visual hallucinations and describing fear-inducing images are at greater risk for negative outcome. Periodic screening may minimize the negative consequences of this disease.

Concentration gradient of noradrenaline from the periphery to the centre of the cornea - A clue to its origin.

We set out to demonstrate that the major source of corneal catecholamines is its neuronal release from intrinsic sympathetic nerves rather than circulating or non-neuronal local production. Three concentric segments (central, intermediate, peripheral) were obtained by double trephination (9.5-7.25 mm) performed on corneas harvested from 3 to 4 month old rabbits and human corneas rejected for transplantation, along with aqueous humour, full iris tissue and blood samples. Endogenous catecholamines were quantified by high pressure liquid chromatography with electrochemical detection (HPLC-ED), and comparison with the uptake of radio-labelled noradrenaline (3H-NA) before and after incubation with cocaine was performed. Results are means ±â€¯SEM. Ratios between enzymatic end products and their substrates were calculated. ANOVA was used for statistical analysis. Catecholamine levels were found to be about one log unit lower in the human cornea than in the rabbit cornea. In the rabbit, dopamine (DA), noradrenaline (NA) and adrenaline (AD) were identified by HPLC-ED in all corneal segments, whilst in the human cornea NA was identified only in the intermediate and peripheral corneal segments, and no AD was found. In the iris and aqueous humour only DA and NA were present. A concentration gradient for NA decreasing from the periphery to the centre of the cornea was identified in both species (NA/DA ratio higher than 1 in the periphery; low AD/NA ratio in all corneal segments), but not for DA or AD. After incubation with 3H-NA all corneal segments and iris tissue showed loading with the aforementioned gradient being reproduced, and a decrease in 3H-NA loading after cocaine was significant only in the peripheral corneal segment and in the iris of both species. Reduction in 3H-NA loading after incubation with cocaine shows that NA in the cornea is mostly of neuronal origin and demonstrates the presence of functional sympathetic nerves (also expectedly found in the iris); the existence of a gradient both for 3H-NA loading and loading reduction after cocaine points to a higher density of fibres in the peripheral cornea.

Regulation of corneal noradrenaline release and topography of sympathetic innervation: Functional implications for adrenergic mechanisms in the human cornea.

Having established a main neuronal origin for noradrenaline (NA) in the cornea, we set out to study the physiologic determinants of its release and to correlate functional findings with sympathetic nerve density and overall topography. Whole corneas were obtained from 3 to 4 month-old rabbits and human donors. Study of prejunctional effects was carried out after incubation with radiolabelled NA (3H-NA). Corneas were superfused with warm aerated amine-free medium with cocaine and hydrocortisone to block subsequent neuronal and extraneuronal NA uptake. Samples were collected every 5 min. Four periods of transmural electrical stimulation were applied to assess evoked release of 3H-NA in the absence and in the presence of alpha-2 adrenoceptor antagonists. Catecholamines were extracted with alumina from the superfusate collected and quantified by high pressure liquid chromatography with electrochemical detection (HPLC-ED). Corneal nerve morphology was studied by immunofluorescence staining with monoclonal antibodies and subsequent confocal microscopy. Corneal lamellar sections were also produced (epithelium, stroma, endothelium) and endogenous NA and adrenaline (AD) were quantified by HPLC-ED. Results are means ±â€¯SEM. ANOVA and t-tests were used for statistical analysis. Ratios between enzymatic end products and their substrates were calculated. In both rabbit and human corneas, electrical stimulation increased the outflow of 3H-NA per minute and per shock. Addition of the alpha-2 adrenoceptor antagonist rauwolscine further increased the electrically-evoked overflow of 3H-NA in a concentration-dependent manner. Immunofluorescence revealed particular staining patterns for sensory and sympathetic fibres, epithelial cells and stromal keratocytes. In human corneal lamellar sections only NA was identified, particularly in the endothelium and epithelium. In the rabbit, concentration of NA was ten times that of AD. Electrically-evoked overflow reflects action potential-induced NA release by sympathetic nerves in the cornea and an alpha-2 adrenoceptor-mediated mechanism for its release is presented. Sympathetic innervation has similar functional relevance in both rabbit and human corneas.

Aflibercept in diabetic macular edema refractory to previous bevacizumab: outcomes and predictors of success.

PURPOSE: To evaluate functional and anatomical outcomes after aflibercept in patients with diabetic macular edema (DME) with poor response to bevacizumab. METHODS: We retrospectively reviewed patients with DME recalcitrant to bevacizumab who were switched to aflibercept between January and December 2015. All patients had a minimal follow-up of three months before the conversion and underwent at least three injections of bevacizumab. Functional outcome consisted in best corrected visual acuity (VA). Anatomical outcomes were demonstrated through central macular thickness (CMT) measured by optical coherence tomography. RESULTS: Forty-nine eyes of 34 subjects were reviewed. Mean VA improved from 0.55 ± 0.32 logMAR to 0.46 ± 0.33 logMAR (p = 0.038). Mean CMT decreased from 473 ± 146 µm to 349 ± 85 µm (p < 0.001). Twelve eyes (24%) demonstrated absence of macular edema after aflibercept. Previous bevacizumab exposure did not correlate with different outcomes. The variation of VA in response to aflibercept was significantly superior in the group with poorer VA before the switch (mean variation of -0.097 ± 0.21 logMAR) when compared to eyes with VA < 0.4 logMAR (mean variation of +0.019 ± 0.090 logMAR; p = 0.036). The same scenario was verified for anatomical outcomes as eyes with poor vision before the switch (≥0.4 logMAR) achieved superior reduction in CMT in response to aflibercept (mean CMT variation of -157 ± 171 µm versus -49.5 ± 39.9 µm; p < 0.01). Pre-switch CMT was a predictor of CMT reduction after switching (B = -0.945; confidence interval 95% -1.1; -0.76; p < 0.001). CONCLUSIONS: Conversion to aflibercept for persistent DME resulted in functional and anatomical improvements and these outcomes were not influenced by previous bevacizumab exposure. Pre-switch CMT was a predictor of anatomical changes after aflibercept.

WAGNER syndrome: anatomic, functional and genetic characterization of a Portuguese family.

PURPOSE: To report the clinical (anatomic and functional) and genetic findings of Wagner Syndrome (WS) in a Portuguese family. METHODS: Nine members of the family agreed to be examined. All had complete clinical eye examinations. The proband and selected patients underwent color fundus photography, spectral domain optical coherence tomography (SD-OCT), automatic static white-on-white computerized perimetry, and electrophysiology assessment (flash ERG, multifocal(mf) ERG and dark adaptometry). A pedigree was constructed based on interviews with known affected subjects. Genomic DNA samples derived from venous blood were collected from all affected family members examined. RESULTS: Twenty-eight family members are affected. This family has the typical features of Wagner Syndrome, namely an empty vitreous cavity with veils, mild myopia and cataract. Four examined patients underwent vitreoretinal surgery due to abnormal peripheral vitreoretinal adhesions with peripheral retinal traction (n = 3). Retinal detachment was observed in 5 of the examined subjects. Four of them occurred between the ages of 5 and 15 years. Chorioretinal atrophy is also a frequent finding which results in moderate to severe visual field and advanced rod-cone dystrophy from younger ages, also confirmed by absence of scotopic function on dark adaptation. The macular dysfunction on mfERG was profound and of early onset. A heterozygous mutation in intron 7 of the VCAN gene (c.4004-1G > A) was found. CONCLUSIONS: We described a rare autosomal dominant vitreoretinopathy with near complete penetrance in a Portuguese family. Abnormal peripheral vitreoretinal adhesions, retinal detachment and chorioretinal atrophy are present in most of the examined individuals at young ages. Early onset of advanced visual field and electrophysiologic abnormalities were observed in this family. We also added relevant information to the literature by reporting our experience in surgical management of Wagner Syndrome patients with, and at risk of, retinal detachment.

Clinical and Microbiological Profile of Bacterial Microbial Keratitis in a Portuguese Tertiary Referral Center-Where Are We in 2015?

OBJECTIVES: To study the microbial profile, antibiotic susceptibility pattern, risk factors, therapeutic trends, and clinical outcomes for microbial keratitis (MK) in a tertiary health care center. METHODS: All cases with suspected bacterial keratitis that were followed at consultation from September 2007 to August 2015 were included. Microbial cultures were obtained and patients were managed following an internal protocol. RESULTS: Two hundred thirty-five patients were included, with a mean age of 50.01±20.73 years. We obtained a 38.4% culture-positive rate, with higher proportion of gram-positives (70.8%). The commonest agents were Staphylococcus aureus (23.1%), Corynebacterium macginleyi (20.0%), and Pseudomonas aeruginosa (13.8%). Fluoroquinolone susceptibility was 97%, with no trend toward its decrease. A total of 95.7% had local risk factors, being trauma and contact lens wear the most common (28.9% each), with different age and pathogens distributions (P<0.001). Topical fluoroquinolones were first-line treatment in 99%, in association with aminoglycosides in 81.6%. Good initial response was registered in 95.9%, but 4.1% needed to step up treatment to fortified antibiotics, mainly if Pseudomonas (P=0.021). Good outcome was achieved in 81.8%, negatively affected by exposure and herpetic keratitis (P<0.001), central location (P=0.01), presence of Tyndall (P<0.001), corneal edema (P<0.001), and worse initial best-corrected visual acuity (P<0.001), but not Pseudomonas isolate (P=0.724). CONCLUSIONS: Gram-positives are the most frequent pathogens and shifting trends in the isolate distribution or emergence of resistant strains were not demonstrated. The susceptibility to first-line antibiotic agents remained high. We suggest a more aggressive approach to P. aeruginosa cases or MK presenting with poor outcome variables.

CHOROIDAL THICKNESS IN MULTISYSTEMIC AUTOIMMUNE DISEASES WITHOUT OPHTHALMOLOGIC MANIFESTATIONS.

PURPOSE: To evaluate choroidal morphology and thickness at the posterior pole of individuals affected by multisystemic autoimmune diseases and without known ophthalmologic manifestations. METHODS: Retrospective cross-sectional study including 75 patients with autoimmune diseases (divided according to their specific disease) and 80 healthy controls. A spectral-domain optical coherence tomography using enhanced depth imaging was performed and choroidal thickness was measured in the center of fovea and at 500 µm intervals along a horizontal section. RESULTS: Lupus patients presented a thicker subfoveal choroid than controls (408.624 vs. 356.536, P < 0.001) and in all the other measurements (P < 0.001 to P = 0.003). Rheumatoid arthritis and other autoimmune diseases had an overall thinner choroid than controls (297.867 vs. 356.536 subfoveally, P = 0.004; P = 0.005-0.019 in other measurements). Results were adjusted for the covariates age (P = 0.007), spherical equivalent (P < 0.001), and systemic steroids dose (P = 0.004). Hypertension (P = 0.102), diabetes mellitus (P = 0.672), time since the beginning of therapy with hydroxychloroquine (P = 0.104) and its cumulative dose (P = 0.307), or use of other immunosuppressives (P = 0.281) had no influence on the mean choroidal thickness. No morphologic abnormalities were found. CONCLUSION: The choroid may be subclinically involved in autoimmune diseases. However, the choroidal response seems to differ depending on the autoimmune disease. Infiltrative mechanisms specific for lupus may justify the thickened choroid found in these patients.

Long-Term Effect of Anti-VEGF Agents on Intraocular Pressure in Age-Related Macular Degeneration.

PURPOSE: To analyze the effect of anti-vascular endothelial growth factor (VEGF) agents on intraocular pressure (IOP) in patients with neovascular age-related macular degeneration (AMD). Materials andMethods: This is a retrospective study that included 72 patients treated unilaterally with anti-VEGF agents according to a pro re nata regimen. Fellow noninjected eyes (n = 72) were used as controls. IOP variation and the development of sustained ocular hypertension (OHT) were assessed both in the injected and in the fellow eyes. RESULTS: While the final IOP was not significantly different between the 2 groups, sustained OHT developed in 4.2% of the injected eyes and 1.4% of the controls. In the study group, no significant IOP variation was noted during follow-up in patients receiving ≤20 injections, but there was a significant increase in IOP with time in more frequently treated patients (p = 0.041). Comparison of both subgroups demonstrated that patients receiving >20 injections suffered significantly greater IOP variation (p = 0.034) during follow-up, and that these patients tended to require IOP-lowering treatment more frequently (p = 0.090). CONCLUSION: Multiple anti-VEGF injections lead to an increase in IOP, although this variation is not sufficient to cause development of OHT in the majority of patients.