The burden of skull base chordomas: insights from a meta-analysis of observational studies.

OBJECTIVE: The aim of this study was to provide a quantitative synthesis of the survival outcomes for patients with skull base chordomas, focusing on the role of 1) the extent of resection (gross-total [GTR] vs non-GTR), 2) the type of surgery (primary vs revision), 3) tumor histology, and 4) the different use of adjuvant therapies (proton beam radiotherapy [PBRT], photon radiotherapy [RT], or none). METHODS: A systematic review with a meta-analysis was conducted following the 2020 PRISMA guidelines. Observational studies describing adult and pediatric patient cohorts harboring skull base chordomas were included. The primary outcome measures were represented by the 5-year overall survival (OS) and progression-free survival (PFS) rates. The main intervention effects were represented by the extent of resection (GTR vs non-GTR), type of surgical excision (primary vs revision surgeries), tumor histology, and the different use of adjuvant therapies (PBRT, RT, or none). The pooled estimates were calculated using random forest models. The risk of bias was evaluated using the Joanna Briggs Institute checklist for case series. RESULTS: Six hundred forty-four studies were identified through a database and register search. After study selection, 51 studies and 3871 patients were included in the meta-analysis. The overall 5-year OS rate was 73%, which increased to 84% among patients undergoing GTR. The overall 5-year PFS rate was 52%, increasing to 74% for patients receiving GTR. The 5-year OS and PFS rates for patients undergoing PBRT were 86% and 71%, compared with 71% and 54% for patients receiving RT, and 55% and 25% when no adjuvant treatments were used. Patients undergoing their first surgery had 2.13-fold greater chances of being disease-free and 1.4-fold greater chances of being alive at 5 years follow-up compared with patients who received a revision surgery. Patients harboring chondroid chordomas had 1.13- and 1.9-fold greater chances of being alive at 5 years compared with patients with conventional and de-differentiated chordomas, respectively. The overall risk of bias was low in the included studies. CONCLUSIONS: The results of this comprehensive meta-analysis highlight the tremendous impact of GTR and adjuvant PBRT on improving OS and PFS of patients harboring skull base chordomas, with better survival rates demonstrated for patients with chondroid tumors. Even in experienced hands, the rate of surgical morbidity remains high. Proper management in high-volume centers is mandatory to reach the expected resection goal at the first surgical attempt and to reduce surgical morbidity. The introduction of the endoscopic endonasal approach was related to improved surgical and functional outcomes.

Clinical and Imaging Biomarkers Associated with Outer Retinal Atrophy Onset in Exudative Age-Related Macular Degeneration: A Real-Word Prospective Study.

INTRODUCTION: Macular neovascularization (MNV) secondary to age-related macular degeneration (AMD) is well managed by anti-vascular endothelial growth factor (anti-VEGF) intravitreal injections. However, outer retinal atrophy represents an unavoidable occurrence detected during follow-up. Several imaging metrics have been proposed as clinically relevant in stratifying the risk of onset of outer retinal atrophy. The main goal of this study is to evaluate the impact of noninvasive imaging metrics on the assessment of outer retinal atrophy onset in a large cohort of eyes with neovascular AMD managed in a real-world setting. METHODS: This study was a prospective, observational, case series. We included patients affected by newly diagnosed neovascular AMD, requiring anti-VEGF intravitreal injections. We collected clinical and imaging data, with a planned follow-up of 24 months. The multimodal imaging protocol included optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. We collected noninvasive imaging metrics and we assessed the relationship with the morphological and functional outcome evaluated at 12-month and 24-month time points. RESULTS: We included 370 eyes of 370 patients with exudative AMD (210 male; mean age 79 ± 8 years). MNV were classified as follows: type 1, 198 (54%); type 2, 89 (24%); polypoidal choroidal vasculopathy, 29 (7%); and type 3, 54 (15%). A total of 120 out of 370 eyes (33%) showed complete outer retinal atrophy at the end of the 2-year follow-up. The presence of intraretinal fluid, thinning of the Sattler choroidal layer, late anti-VEGF switch, the overall number of anti-VEGF injections, and the perfusion characteristics of the MNV were found to be the most relevant factors associated with the onset of outer retinal atrophy. The other collected metrics were found to be less clinically relevant, also showing no cumulative effect in the multivariate analysis (p > 0.05). CONCLUSIONS: We identified imaging metrics significantly associated with the 2-year risk onset of outer retinal atrophy. These metrics might pave the way for the development of future customized anti-VEGF treatment strategies.

Inner retinal thickness in Stargardt disease.

PURPOSE: To analyze the alterations at the level of the inner retina in patients affected by Stargardt disease (STGD1). METHODS: Cross-sectional investigation involving STGD1 patients with genetically confirmed diagnosis, who underwent optical coherence tomography (OCT), optical coherence tomography angiography (OCTA), and microperimetry. RESULTS: Overall, 31 patients (62 eyes) with genetically confirmed STGD1 were included in the study. Mean inner retinal thickness, vessel density of plexa, and retinal sensitivity resulted significantly reduced in STGD patients, compared with healthy controls (p < 0.05), both in the outer and in the inner ETDRS rings. Overall, 43% of eyes revealed an inner retinal thinning, whereas 21% and 35% showed a thicker or within normal range inner retina. CONCLUSIONS: Inner retina is irregularly altered in STGD1, showing variable quantitative alterations as detected on OCT. Inner retinal status might represent a useful biomarker to better characterize STGD1 and to ascertain the effects of new treatment approaches.

New insights in the multimodal imaging of retinitis pigmentosa.

Retinitis pigmentosa (RP) is a group of inherited rod-cone dystrophies, noted for a high genotypical and phenotypical heterogeneity.Traditionally, VA, visual field, and electroretinography have been used to assess RP progression. However, visual acuity and visual field tests are essentially subjective and, especially in the late stages of the disease, are unable to confidently reveal minor progression. Therefore, there is a need for novel examination modalities that rely on quantitative, structural measurements. In this regard, several non-invasive imaging techniques have been studied, including spectral-domain optical coherence tomography, optical coherence tomography angiography, and fundus autofluorescence. By correlating surrogate biomarkers with functional measurements of the disease, these techniques may be able to develop reliable outcome meters that can be used to gain a deeper understanding of the underlying causes of the disease and to assess the effectiveness of therapy even before an actual loss of vision occurs.In this review, we will summarize the recent imaging findings and biomarkers that have been identified in RP patients. Our goal is to provide information that can promptly aid in selecting patients for clinical trials and new gene therapies, monitoring the disease progression, and evaluating treatment outcomes.

Non-vasogenic cystoid maculopathy in autosomal recessive bestrophinopathy: novel insights from NIR-FAF and OCTA imaging.

BACKGROUND: Autosomal Recessive Bestrophinopathy (ARB) is an inherited retinal disease caused by biallelic mutations in the BEST1 gene. Herein, we report the multimodal imaging findings of ARB presenting with cystoid maculopathy and investigate the short-term response to combined systemic and topical carbonic anhydrase inhibitors (CAIs). MATERIAL AND METHODS: An observational, prospective, case series on two siblings affected by ARB is presented. Patients underwent genetic testing and optical coherence tomography (OCT), blue-light fundus autofluorescence (BL-FAF), near-infrared fundus autofluorescence (NIR-FAF), fluorescein angiography (FA), MultiColor imaging, and OCT angiography (OCTA). RESULTS: Two male siblings, aged 22 and 16, affected by ARB resulting from c.598C>T, p.(Arg200*) and c.728C>A, p.(Ala243Glu) BEST1 compound heterozygous variants, presented with bilateral multifocal yellowish pigment deposits scattered through the posterior pole that corresponded to hyperautofluorescent deposits on BL-FAF. Vice versa, NIR-FAF mainly disclosed wide hypoautofluorescent areas in the macula. A cystoid maculopathy and shallow subretinal fluid were evident on structural OCT, albeit without evidence of dye leakage or pooling on FA. OCTA demonstrated disruption of the choriocapillaris throughout the posterior pole and sparing of intraretinal capillary plexuses. Six months of combined therapy with oral acetazolamide and topical brinzolamide resulted in limited clinical benefit. CONCLUSIONS: We reported two siblings affected by ARB, presenting as non-vasogenic cystoid maculopathy. Prominent alteration of NIR-FAF signal and concomitant choriocapillaris rarefaction on OCTA were noted in the macula. The limited short-term response to combined systemic and topical CAIs might be explained by the impairment of the RPE-CC complex.

Multimodal imaging in Best Vitelliform Macular Dystrophy: Literature review and novel insights.

Best Vitelliform Macular Dystrophy (BVMD) is a dominantly inherited retinal disease caused by dominant variants in the BEST1 gene. The original classification of BVMD is based on biomicroscopy and color fundus photography (CFP); however, advancements in retinal imaging provided unique structural, vascular, and functional data and novel insights on disease pathogenesis. Quantitative fundus autofluorescence studies informed us that lipofuscin accumulation, the hallmark of BVMD, is unlikely to be a primary effect of the genetic defect. It could be due to a lack of apposition between photoreceptors and retinal pigment epithelium in the macula with subsequent accumulation of shed outer segments over time. Optical Coherence Tomography (OCT) and adaptive optics imaging revealed that vitelliform lesions are characterized by progressive changes in the cone mosaic corresponding to a thinning of the outer nuclear layer and then disruption of the ellipsoid zone, which are associated with a decreased sensitivity and visual acuity. Therefore, an OCT staging system based on lesion composition, thus reflecting disease evolution, has been recently developed. Lastly, the emerging role of OCT Angiography proved a greater prevalence of macular neovascularization, the majority of which are non-exudative and develop in late disease stages. In conclusion, effective diagnosis, staging, and clinical management of BVMD will likely require a deep understanding of the multimodal imaging features of this disease.

Association of Circulating Antiretinal Antibodies With Clinical Outcomes in Retinitis Pigmentosa.

Purpose: To determine if circulating antiretinal antibodies (ARAs) differ between patients affected by retinitis pigmentosa (RP) and control participants and to assess whether ARAs are associated with clinical outcomes in patients with RP. Methods: Cross-sectional study involving a group of patients clinically diagnosed with RP and a control group of healthy participants. Serum autoantibodies against enolase, heat shock protein 70 (HSP70), and carbonic anhydrase II (CAII) were tested in all participants using Jess capillary Western blot. We compared ARA prevalence between the RP and control groups and investigated the association of serum ARA positivity with macular edema and vitreomacular disorders in patients affected by RP. Results: Thirty-six patients affected by RP and a control group of 39 healthy individuals were included. Overall, at least one ARA positivity was detected in 89% and 80% of participants in the RP and control groups, respectively. We observed a similar prevalence of anti-CAII and anti-enolase ARA between patients and controls (P = 0.87 and P = 0.35, respectively). Sera from patients with RP tested positive for anti-HSP70 ARAs more frequently than those from controls (53% vs. 36%), albeit without reaching statistical significance (P = 0.29). Among the 72 eyes with RP, 25% presented with macular edema (most often bilateral) and 33% with epiretinal membrane and/or lamellar macular hole. None of the three ARAs was associated with an increased risk of any macular complications in eyes affected by RP (all P > 0.05). Conclusions: The prevalence of circulating ARAs against enolase, HSP70, and CAII is similar between patients affected by RP and healthy individuals. Our results provide evidence against the association of ARAs with macular edema and vitreomacular interface disorders in RP.

Acute atrophic evolution of drusenoid pigment epithelium detachment after photobiomodulation.

PURPOSE: To report the acute onset of macular atrophy soon after photobiomodulation (PBM) administration in a patient with intermediate age-related macular degeneration (AMD). METHODS: Optical coherence tomography (OCT) was performed in the study eye before and after PBM. RESULTS: A patient with drusenoid pigment epithelium detachment (D-PED) underwent PBM. A few weeks after PBM the D-PED collapsed, resulting in incomplete retinal pigment epithelium and outer retinal atrophy with visual acuity worsening. CONCLUSION: Thinning of the outer retinal layers over a D-PED and posterior hypertrasmission may represent bad prognostic factors for PBM, accelerating the lesion's natural history towards atrophic evolution.

Microvascular decompression for trigeminal neuralgia: a single-center experience with 516 cases, including 32 patients with multiple sclerosis.

BACKGROUND AND OBJECTIVES: To evaluate the effectiveness and long-term pain relief of microvascular decompression (MVD) for "typical" trigeminal neuralgia (TN), including patients affected by multiple sclerosis (MS). METHODS: Between January 2011 and December 2022, 516 consecutive patients presenting with trigeminal neuralgia and a diagnosed neurovascular conflict at MRI underwent microvascular decompression surgery in our neurosurgery department. Ten surgeons with different ages and experiences performed the surgical procedures. Pain improvement, re-operation rate, and complication rates were retrospectively collected and analyzed. RESULTS: 516 patients were included (214 males 302 females, ranging from 12 to 87 years), including 32 patients with multiple sclerosis. Neurovascular compression was found in all cases during surgery. Barrow Neurological Institute pain intensity scale with a score of I was achieved in 404 patients (78,29%), a score II or III was obtained in 100 cases (19,37%) and a score of IV and V in 12 patients (2,32%). In the multiple sclerosis subset of patients, a BNI score of I was achieved in 21/32 (65.62%). The pain recurrence rate of our series was 15.11%. The follow-up for all patients was at least of 13 months, with a mean follow-up of 41.93 months (± 17.75 months, range 13-91 months). Neither intraoperative mortality nor major intra-operative complications occurred in the analyzed series. The re-operation rate was 12.98%. Thermorhizotomy, percutaneous balloon compression, cyber-knife radiosurgery, or new MVD were the surgical techniques utilized for re-operations. CONCLUSIONS: MVD may be considered an effective and safe surgical technique for TN, and in patients affected by multiple sclerosis, it may be proposed even if a less favorable outcome has to be expected with respect to classic TN patients. Larger studies focusing on the relation of multiple sclerosis with neurovascular compression are required.

Case Report: Opposite Tumoral and Hormonal Responses to Low-dose Pasireotide in Cushing's Disease.

BACKGROUND: Pasireotide is a multireceptor somatostatin analogue approved for the treatment of patients with Cushing's disease (CD) who are ineligible or poor candidates for pituitary surgery. Here we present a patient with severe recurrent CD who was treated with pasiretide and showed opposite results between hormonal levels and pituitary tumour size. CASE PRESENTATION: A 54-year-old woman was diagnosed with CD, a first surgical transsphenoidal procedure was performed at the time of diagnosis, and the disease recurred seven years later. She underwent a second transsphenoidal surgery, but despite apparent complete removal of the adenoma, the hypercortisolism worsened. Magnetic resonance imaging showed a tiny remnant of the adenoma adjacent to the cavernous sinus, and ketoconazole was started at a dose of 800 mg/day. Due to the persistence of pathological urinary free cortisol levels, 600 µg bid pasireotide was added. The combination therapy induced first normalisation of urinary free cortisol and later hypoadrenalism, so that ketoconazole was discontinued and pasireotide was maintained. A marked clinical improvement was achieved with pasireotide. Adrenal insufficiency persisted despite progressive tapering of the pasireotide dose to 150 mg once daily. Pituitary magnetic resonance imaging performed at 12 and 24 months during low-dose pasireotide treatment showed a few millimetres increase of the remnant. CONCLUSIONS: This report suggests that CD Pas induces an opposite effect between hormonal profile and increase of pituitary tumor size. This peculiar phenomenon may be a consequence of the unusually low doses of pasireotide needed to control hormonal hypersecretion.

Pigmented paravenous chorioretinal atrophy: Updated scenario.

Pigmented paravenous chorioretinal atrophy (PPCRA) is an uncommon form of chorioretinal atrophy characterized by perivenous aggregations of pigment clumps associated with peripapillary and radial zones of retinal pigment epithelial atrophy that are distributed along the retinal veins. Most patients are asymptomatic, and evidence suggest that PPCRA is slowly progressing. Unless macular involvement is present, the majority of patients usually retain a normal visual function. Our ability to diagnose PPCRA has recently improved thanks to multimodal imaging, especially with the advent of ultra-widefield (UWF) imaging. Blood tests and functional and genetic testing can help with the correct differential diagnosis of pseudo-PPCRA or other disorders with similar characteristics. Although the cause of PPCRA is unknown, it is possible that it has a genetic basis. In this review we provide a summary of the multimodal imaging characteristics of PPCRA, and discuss its possible pathogenesis, based on the genes that have been associated with this disease.

The Clinical Role of the Choroidal Assessment in High Myopia: Characteristics and Association With Neovascular and Atrophic Complications.

Purpose: To investigate the clinical utility of choroidal quantitative assessment associated with the presence of macular neovascularization (MNV) or atrophy in high myopia. Methods: The study was designed as a retrospective case series with two-year follow-up. We measured choroidal thickness (CT) and the presence and subtype of dome-shaped macula (DSM). In DSM eyes we also calculated the presence and type of choroidal deepening (CD). The eyes were categorized as Subgroup 1 (high myopia without complications), Subgroup 2 (high myopia complicated by MNV), and Subgroup 3 (high myopia complicated by macular or posterior pole atrophy). Main outcome measures were the detection of significant CT cutoffs associated with the three subgroups of eyes and the clinical impact of DSM and CD subtypes. Results: Our cohort (190 eyes affected by high myopia) was categorized as Subgroup 1 (66 eyes), Subgroup 2 (72 eyes) and Subgroup 3 (52 eyes). Baseline CT values allowed to separate the subgroups with myopic-related complications (area under the curve = 0.85; P < 0.05). In Subgroup 1, vertical DSM was the most frequent (54%), with CD absence characterizing the 46% of cases. Round DSM was the most represented subtype in Subgroup 2 (49%), with 55% of sub-dome CD subtypes; in these cases, MNV resulted always localized in the fovea. Subgroup 3 equally shown horizontal or vertical DSM (53% and 47%, respectively), with 80% of cases showing peri-dome CD. Conclusions: Choroidal quantitative assessment can categorize three high myopia subgroups. MNV subgroup is characterized by intermediate choroidal thinning and higher prevalence of round DSM with sub-dome CD.

The Localization of Intraretinal Cysts Has a Clinical Role on the 2-Year Outcome of Neovascular Age-Related Macular Degeneration.

OBJECTIVE: To assess the relationship between ≥ 1 localizations of intraretinal fluid (IRF) within retinal layers and the 2-year outcome in a cohort of neovascular age-related macular degeneration (AMD) eyes. DESIGN: Retrospective case series. PARTICIPANTS: Two hundred forty-three eyes of 243 AMD patients affected by type 1 and type 2 macular neovascularization (MNV). METHODS: We analyzed data considering MNV onset, 1-year, and 2-year timepoints. Optical coherence tomography images were used to classify MNV types, distinguish different types of fluids and assess IRF localization within retinal layers. A subcohort of eyes were also analyzed by OCT angiography. MAIN OUTCOME MEASURES: The association between IRF cyst localization and both visual outcome and onset of outer retinal atrophy at 2-year follow-up. RESULTS: Macular neovascularizations were distributed as type 1 (69%) and type 2 (31%). The mean number of intravitreal injections was 7 ± 2 at 1-year follow-up and 5 ± 2 at 2-year follow-up. Baseline best-corrected visual acuity was 0.4 ± 0.3 logarithm of the minimum angle of resolution, improving to 0.3 ± 0.4 at 2-year follow-up (P < 0.01). Outer retinal atrophy occurred in 24% of cases at 1 year and 39% of cases at 2-year follow-up. Intraretinal fluid localizations at the level of IPL-INL and OPL-ONL at baseline were associated with the worst functional and anatomical outcome. Moreover, the presence of IRF at baseline was associated with greater impairment of the intraretinal vascular network. CONCLUSIONS: The localization of IRF at the level of IPL-INL and OPL-ONL retinal layers represents a negative prognostic biomarker for the morphologic and functional outcomes of neovascular AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Skull Base Meningiomas.

Skull base meningiomas are among the most challenging meningiomas to treat clinically due to their deep location, involvement or encasement of adjacent essential neurovascular structures (such as key arteries, cranial nerves, veins, and venous sinuses), and their often-large size prior to diagnosis. Although multimodal treatment strategies continue to evolve with advances in stereotactic and fractionated radiotherapy, surgical resection remains the mainstay of treatment for these tumors. Resection of these tumors however is challenging from a technical standpoint, and requires expertise in several skull-base surgical approaches that rely on adequate bony removal, minimization of brain retraction, and respect for nearby neurovascular structures. These skull base meningiomas originate from a variety of different structures including, but are not limited to: the clinoid processes, tuberculum sellae, dorsum sellae, sphenoid wing, petrous/petroclival area, falcotentorial region, cerebellopontine angle, and foramen magnum. In this chapter, we will cover the common anatomical areas in the skull base from which these tumors arise, and the specific or optimal surgical approaches and other treatment modalities for meningiomas in these such locations.

Surgical Therapy of Non-Skull Base Meningiomas.

In a previous chapter, the surgical management of skull base meningiomas were discussed. However, the most common meningiomas that are diagnosed and operated on are non-skull base tumors located in the parasagittal/parafalcine region and convexity, and more rarely along the tentorium, and in an intraventricular location. These tumors present their own unique set of challenges given their unique anatomy and tend to be more biologically aggressive compared to skull base meningiomas, thereby reinforcing the importance of obtaining a gross total resection if possible, in order to delay recurrence. In this chapter we will cover the surgical management of non-skull base meningiomas with technical considerations for tumors located in each of the anatomical areas listed above.

Peripheral Retinal Involvement in Extensive Macular Atrophy with Pseudodrusen-Like Deposits.

PURPOSE: To describe the alterations of the peripheral retina in extensive macular atrophy with pseudodrusen-like deposits (EMAP) by means of ultrawidefield fundus photography (UWFFP) and ultrawidefield fundus autofluorescence (UWF-FAF). STUDY DESIGN: Prospective, observational case series. PARTICIPANTS: Twenty-three patients affected by EMAP. METHODS: Each patient underwent best-corrected visual acuity (BCVA) measurement, UWFFP, and UWF-FAF. The area of macular atrophy, as well as the pseudodrusen-like deposits and peripheral degeneration, were assessed using UWF images, at baseline and over the follow-up. MAIN OUTCOME MEASURES: The assessment of the clinical patterns of both pseudodrusen-like deposits and peripheral retinal degeneration. Secondary outcomes included assessing macular atrophy by means of UWFFP and UWF-FAF, and tracking progression over the follow-up. RESULTS: Twenty-three patients (46 eyes) were included, of whom 14 (60%) were female. Mean age was 59.0 ± 5 years. Mean BCVA at baseline was 0.4 ± 0.4, declining at a mean rate of 0.13 ± 0.21 logarithm of the minimum angle of resolution/year. Macular atrophy at baseline was 18.8 ± 14.2 mm2 on UWF-FAF, enlarging at a rate of 0.46 ± 0.28 mm/year, after the square root transformation. Pseudodrusen-like deposits were present in all cases at baseline, and their detection decreased over the follow-up. Three main types of peripheral degeneration were identified: retinal pigment epithelium alterations, pavingstone-like changes, and pigmented chorioretinal atrophy. Peripheral degeneration progressed in 29 eyes (63.0%), at a median rate of 0.7 (interquartile range, 0.4-1.2) sectors/year. CONCLUSIONS: Extensive macular atrophy with pseudodrusen-like deposits is a complex disease involving not only the macula, but also the midperiphery and the periphery of the retina. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Foveal Eversion is Associated with High Persistence of Macular Edema and Visual Acuity Deterioration in Retinal Vein Occlusion.

INTRODUCTION: Foveal eversion (FE) is a recently described optical coherence tomography (OCT) finding associated with negative outcome in diabetic macular edema. The main goal of the present study was to investigate the role of the FE metric in the diagnostic workup of retinal vein occlusion (RVO). METHODS: This study was a retrospective, observational case series. We included 168 eyes (168 patients) affected by central RVO (CRVO) and 116 eyes (116 patients) affected by branch (RVO). We collected clinical and imaging data from CRVO and BRVO eyes affected by macular edema with a minimum follow-up of 12 months. On structural OCT, we classified FE as pattern 1a, characterized by thick vertical intraretinal columns, pattern 1b, presenting thin vertical intraretinal lines, and pattern 2, showing no signs of vertical lines in the context of the cystoid macular edema. For statistical purposes, we considered data collected at baseline, after 1 year and at the last follow-up. RESULTS: The mean follow-up was 40 ± 25 months for CRVO eyes and 36 ± 24 months for BRVO eyes. We found FE in 64 of 168 CRVO eyes (38%) and in 25 of 116 BRVO eyes (22%). Most of the eyes developed FE during the follow-up. For CRVO eyes, we found 6 eyes (9%) with pattern 1a, 17 eyes (26%) with pattern 1b and 41 eyes (65%) with pattern 2. Of those BRVO eyes with FE, we found 8 eyes (32%) with pattern 1a + 1b and 17 eyes (68%) with pattern 2. In both CRVO and BRVO the presence of FE was significantly associated with higher persistence of macular edema and worse outcome, with FE pattern 2 representing the most severe condition. Remarkably, FE patterns 1a and 1b were characterized by BCVA stability over the follow-up, whereas FE pattern 2 showed significant bestcorrected visual acuity (BCVA) worsening at the end of the follow-up. CONCLUSIONS: FE can be considered a negative prognostic biomarker in RVO, associated with higher persistence of macular edema and worse visual outcome. Müller cell impairment might represent the pathogenic mechanism leading to the loss of macular structural support and impairment of fluid homeostasis.

ACTH Stimulation Test for the Diagnosis of Secondary Adrenal Insufficiency: Light and Shadow.

Secondary Adrenal Insufficiency (SAI) is a condition characterized by inappropriately low ACTH secretion due to a disease or injury to the hypothalamus or the pituitary. The evaluation when suspected is often challenging for the non-specific symptoms, the rarity of the disease, and the pitfalls associated with laboratory tests. A prompt and correct diagnosis of SAI is essential because although an adequate hormonal replacement therapy could be lifesaving, inappropriate life-long therapy with steroids can be harmful. The gold standard test for assessing the hypothalamus-pituitary-adrenal axis (HPA) is the insulin tolerance test (ITT), but due to safety issues is not widely used. Conversely, the ACTH stimulation test is a safer and well-tolerated tool for SAI diagnosis. However, data about its diagnostic accuracy show great variability due to both technical and interpretative aspects, such as dose, route of administration, the timing of the test, and assay used for cortisol measurements. Consequently, the clinical background of the patient and the pretest probability of HPA axis impairment become of paramount importance. We aimed to summarize the recent literature evidence in the conduction and interpretation of the ACTH stimulation test for the diagnosis of SAI to provide updated insights on its correct use in clinical practice.

Deep Capillary Plexus as Biomarker of Peripheral Capillary Nonperfusion in Central Retinal Vein Occlusion.

Purpose: To identify the vascular biomarkers of peripheral capillary nonperfusion in patients affected by naive central retinal vein occlusion (CRVO), and to analyze their changes over the follow-up. Study Design: Consecutive prospective case series with a planned follow-up of 2 years. Participants: Thirty-five patients affected by CRVO and 35 healthy gender- and age-matched subjects were enrolled in the study. Methods: Ophthalmic examination included best corrected visual acuity (BCVA), ultrawidefield fluorescein angiography (UWFFA), OCT, and OCT angiography (OCTA). Main Outcome Measures: Vessel density (VD) at the superficial capillary plexus and deep capillary plexus (DCP) were calculated on OCTA images. The ischemic index (ISI) was calculated on UWFFA. Results: The mean baseline ISI was 37%, increasing to 40% at the end of the follow-up, whereas it was 4.9% in the patients' fellow eyes and 4.5% in the control group with no change over the follow-up. OCT angiography revealed VD reduction in the DCP, considering both 3 × 3 mm and 12 × 12 mm scans. The correlation analyses revealed that DCP VD was the only parameter showing a statistically significant correlation with the foveal avascular zone (FAZ) area, BCVA, and ISI. Conclusions: Deep capillary plexus VD impairment is detectable in all CRVO cases, variably involving both the central retina (with enlarged FAZ) and the periphery (with VD reduction in the peripheral retina). The severity of DCP VD reduction has correlates with various clinical markers. Deep capillary plexus VD may represent a crucial biomarker to characterize CRVO, and further studies are necessary to identify the cutoff thresholds for the different clinical manifestations.