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Purpose: To detect the vessel density of choriocapillaris (CC) vascular network in eyes affected by choroidal osteoma and in eyes complicated by macular neovascularization (MNV), using optical coherence tomography angiography (OCTA)., Methods: In this retrospective study, twenty-eight eyes of 28 patients were divided into three groups: group 1 including patients with calcified choroidal osteoma, group 2 including patients with decalcified choroidal osteoma, and group 3 including patients with decalcified choroidal osteoma complicated by MNV. OCTA analyzed the vessel density of CC in these lesions localized in the peripapillary region., Results: We enrolled 12 eyes with calcified choroidal osteoma, 11 eyes with decalcified choroidal osteoma, and 5 eyes with decalcified choroidal osteoma complicated by MNV. The eyes with decalcified choroidal osteoma and MNV revealed a statistically significant reduction in vessel density of the CC respect to the other groups (p < 0.001). Moreover, the vessel density of CC in decalcified choroidal osteoma was significantly reduced compared to calcified choroidal osteoma (p < 0.001)., Conclusions: OCTA allowed a quantitative evaluation of choriocapillaris vessel density in choroidal osteoma, in order to detect the changes of this vascular network, which could lead to the development of MNV. Therefore, OCTA could be a new diagnostic tool in the clinical management of the choroidal osteoma., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT05342324., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To compare optical coherence tomography angiography (OCTA) and indocyanine green angiography (ICGA) in terms of reliability in detecting dark halo in patients affected by age-related macular degeneration (AMD) complicated with type 1 macular neovascularization (MNV)., Methods: Eighty-nine eyes of 89 patients were analyzed at the University of Naples Federico II between January 2018 and October 2021. Each patient underwent a complete ophthalmological evaluation including fluorescein angiography, ICGA, spectral domain optical coherence tomography (SD-OCT), and OCTA. OCTA and ICGA images of dark halo were compared. The paired Student's test and intraclass correlation coefficients were used to evaluate the differences in dark halo measurements between OCTA and ICGA images., Results: Thirty-six eyes of 36 patients were included in this prospective study. Dark halo area was significantly larger in OCTA than in ICGA (1.49 ± 1.8 mm 2 vs. 0.54 ± 0.5 mm 2 ; p = 0.001). Moreover, the agreement between the two types of devices for measuring dark halo areas was poor, with a low intraclass coefficient correlation (0.397)., Conclusion: OCTA could be a useful and necessary tool to investigate dark halo in neovascular AMD due to its ability to visualize the areas of reduced vessel density around MNV in greater detail compared to ICGA., Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT05108285., (© 2022. The Author(s).)

Purpose: This study aims to investigate the safety and efficacy of short-term treatment for ocular surface disease (OSD) with topical low-dose (1,005 mg) preservative-free hydrocortisone in one hundred patients with and without glaucoma., Methods: This was an open label non-randomized clinical trial. Patients with OSD with and without primary open-angle glaucoma (POAG) received topical low-dose (1,005 mg) preservative-free hydrocortisone twice daily in each eye for 2 weeks. All patients underwent a complete ophthalmological examination at baseline (T0) and at 1 (T1) and 2 (T2) weeks post-treatment. At each visit, the intraocular pressure (IOP) and the ocular surface disease index (OSDI) questionnaire scores were recorded; the Schirmer test was performed only at T0 and T2., Results: The OSDI score significantly decreased in both the POAG and no-POAG groups (both p < 0.0001) after hydrocortisone treatment, with no difference between the two groups (p = 0.72). There were no significant differences in IOP and Schirmer test results between T0 and T2 in both treatment groups (p = 0.68 and p = 0.83, respectively)., Conclusions: Topical low-dose (1,005 mg) preservative-free hydrocortisone is safe and effective for improving OSD symptoms both in patients with and without POAG., Trial Registration: The trial was registered at clinicaltrials.gov under NCT04536129 on 01/09/2020 ("retrospectively registered")., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To describe a distinct vitreomacular interface disorder (VMID) termed Foveal Abnormality associated with epiretinal Tissue of medium reflectivity and Increased blue-light fundus Autofluorescence Signal (FATIAS)., Methods: A case series including forty-seven eyes of 47 patients. The included eyes must present an irregular foveal contour on optical coherence tomography (OCT) and a pathologically increased autofluorescent signal at the fovea on blue-light fundus autofluorescence (B-FAF). Main outcome measures were morphologic characteristics of the lesions, logarithm of minimum angle of resolution (logMAR) best-corrected visual acuity (BCVA), and central foveal thickness (CFT)., Results: The following two types of FATIAS were identified: (1) the step type characterized by an asymmetric contour of the foveal pit and by a tissue of medium reflectivity on the foveal surface and (2) the rail type characterized by a shallow foveal pit and a rail of tissue of medium reflectivity on the foveal surface. The outer retinal bands were continuous in all cases. Both types presented with an area of increased B-FAF signal, usually bilobed in the step type and round and centered on the foveal pit in the rail type. LogMAR BCVA was 0.09 ± 0.1 and 0.1 ± 0.1 (P = 0.91), and CFT was 197.8 ± 9.7 and 202.2 ± 13.2 (P = 0.19) in the step and in the rail group, respectively., Conclusions: We describe a distinct VMID named FATIAS. Two types of FATIAS may be appreciated with SD-OCT and B-FAF analyses, the step and the rail type. Both are characterized by abnormal foveal contour and autofluorescence signal.

Purpose: To study the natural history and morphologic characteristics of lamellar macular holes (LMHs) in the eyes with pathological myopia., Methods: Retrospective observational case series of 44 eyes of 44 patients examined at a single institutional vitreoretinal practice. The included eyes must present an irregular foveal contour and schitic or cavitated lamellar separation of neurosensory retina on spectral-domain optical coherence tomography (SD-OCT) and an area of increased autofluorescence on blue fundus autofluorescence (B-FAF) to be included. Presence of retinoschisis and posterior staphyloma, posterior vitreous status, changes of logarithm of minimum angle of resolution best-corrected visual acuity (BCVA), and changes of morphologic characteristics were evaluated., Results: The mean follow-up period was 50.1 ± 28.9 months; 75% of the enrolled patients were female. At baseline, a standard epiretinal membrane (ERM) was detected in 93.2%, lamellar hole-associated epiretinal proliferation (LHEP) in 75%, and concomitant ERM and LHEP in 68.2% of the eyes, respectively. Visual acuity did not correlate with LMH diameters but correlated with central foveal thickness (p < 0.001). During the follow-up, the morphologic and functional parameters studied were relatively stable/improved in 60% of the eyes independently from the associated epiretinal material. Four eyes evolved to full-thickness (FT) MHs whereas spontaneous improvement was observed in five cases., Conclusions: LMHs in highly myopic eyes are more prevalent in females, are frequently associated with ERM and LHEP, and show substantial stability of BCVA and the anatomic parameters evaluated with B-FAF and SD-OCT over years-long follow-up.

Purpose: To compare the anatomic and functional outcome of two variants of the inverted internal limiting membrane (I-ILM) flap technique for idiopathic macular holes (IMH) larger than 400 µm., Methods: Twenty-seven consecutive patients undergoing PPV for IMH were randomly assigned to different variants of I-ILM technique: the Cover group included 14 patients in which the I-ILM was folded upside-down over the MH as a single layer while the Fill group enrolled 13 patients in which the I-ILM was folded within the MH in multiple layers., Results: MH closed in 12/14 Cover and in 13/13 Fill eyes (84.6 vs. 100%, p = 0.14; n.s.). Vision at 1 month was Snellen 0.44 ± 0.17 vs. 0.28 ± 0.21 (p = 0.05) and 0.48 ± 0.20 vs. 0.37 ± 0.25 (n.s.) at 3 months. IS/OS line interruption width was 463 ± 385 vs. 602 ± 210 µm, respectively, at 1 month (n.s.) and 602 ± 210 vs. 563 ± 209 µm at 3 months (n.s.). The Cover group showed outer retina cystic changes more often (p < 0.01). MH over 700 µm closed in 0/2 and in 2/2 cases, respectively, in the Cover and Fill groups (0.045)., Conclusions: Cover and Fill I-ILM techniques allowed similar closure rates and post-operative vision at 3 months. The Cover group showed better anatomical restoration and vision at 1 month while the Fill technique might be more efficient in closing larger MHs.

Purpose: To compare visual and anatomical outcomes between half-dose photodynamic therapy (hd-PDT) and 689 nm laser therapy (689-LT) in chronic central serous chorioretinopathy (CSC)., Methods: Forty eyes of 40 patients with symptomatic chronic CSC were randomized in a 1:1 ratio to receive either hd-PDT or 689-LT delivering 95 J/cm 2 via an intensity application of 805 mW/cm 2 over 118 s. Best-corrected visual acuity (BCVA) and spectral-domain optical coherence tomography findings were compared between the two treatment groups., Results: Mean CSC duration was 17.1 ± 6.66 weeks and 18.7 ± 7.46 weeks in the hd-PDT and 689-LT groups respectively. Both groups showed significant BCVA improvements, as well as reductions in central retinal and subfoveal choroidal thickness. Although hd-PDT led to a faster reduction in central retinal thickness, no significant differences were recorded between groups for any other measured parameter at any time point. Complete photoreceptor recovery was observed in eight and seven eyes in the hd-PDT and 689-LT groups respectively., Conclusions: Both hd-PDT and 689-LT were effective at treating chronic CSC. Further studies are warranted to evaluate long-term safety and efficacy.

Background: To demonstrate the efficacy of intravitreal ranibizumab (IVR) in combination with reduced-fluence photodynamic therapy (RF-PDT) in patients with choroidal neovascularization (CNV) secondary to pathologic myopia., Methods: Sixty patients affected by myopic CNV (mCNV) were randomized to receive either ranibizumab 0.5 mg monotherapy (RM; n = 20), standard fluence PDT (SF-PDT, n = 20) or RF-PDT combination therapy (n = 20). Subsequently, IVR was injected as needed. All patients were evaluated for 48 weeks., Results: Mean BCVA change at 48 weeks was + 0.2 and +15 letters with SF or RFPDT plus ranibizumab, respectively, compared with +16.8 letters with RM. At 48 weeks, mean central foveal thickness (CFT) decrease from baseline was 58 ± 15 μm, 91.4 ± 43.8 μm, and 85 ± 41.5 μm for the verteporfin SF, RF and RM groups, respectively. Macular sensitivity improvement was + 0.4 db, + 1.9 dB and + 2.7 dB for the verteporfin SF, RF and RM groups, respectively., Conclusions: Ranibizumab monotherapy or combined with RF-PDT improved BCVA and macular sensitivity in patients affected by mCNV, whereas CFT results were reduced. SF-PDT combination regimen mostly stabilized vision at 48 weeks. Among all groups, the RF-PDT seemed to reduce the number of ranibizumab retreatments.

Background: To describe the histological features of failed gold micro shunts (GMS) in unsuccessful implantations for refractory primary open-angle glaucoma (POAG)., Methods: This was an interventional case series study. Five eyes of five glaucomatous patients with unsuccessful GMS implantation underwent shunt removal. Each device was sectioned into three portions: proximal or anterior chamber (AC) portion, middle or scleral portion and distal or suprachoroidal (SC) portion. The histological analysis was performed throughout the whole extent of the shunt, describing both the inner spaces and the outer surface., Results: At the moment of removal all devices were correctly located into the SC space and in AC, with the exception of a case presenting corneal endothelial contact. The mean intra-ocular pressure before GMS removal was 30.4 ± 5.3 mmHg, and the mean time of GMS removal after implantation was 6.8 ± 2.5 months. No significant histological differences were documented among the five analyzed devices. The main feature was the presence of a thick connective capsule-like reaction surrounding both the proximal and distal ends and invading the posterior and anterior grid holes, whereas a more loosely arranged connective tissue was observed within the inner channels. Signs of surface fibrosis of the middle-scleral portion and inflammatory cell infiltration of the device were not documented in any of the cases., Conclusions: Failed GMS implantations presented connective tissue filling all the inner spaces and creating a thick fibrotic capsule surrounding the ends of the device. This modification isolated the GMS from the AC and SC space, impeding aqueous flows throughout the shunt.

Background: To report 12-month follow-up results of 156 eyes treated with anti-VEGF for subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration, and to verify the efficacy of this treatment in terms of functional results and changes of morphology of choroidal membrane for the different types of choroidal neovascularization analyzed., Methods: This prospective case series study included subjects with different forms of subfoveal CNV. After the first intravitreal injection of 1.25 mg bevacizumab at baseline, re-injections of bevacizumab were scheduled at least 4 weeks after initial treatment following standardized criteria., Results: One hundred and fifty six patients were divided into two study groups: 60 eyes with classic CNV (group C) and 96 eyes with occult CNV (group O). The improvement in BCVA was greater in group C than group O, although the difference was not statistically significant (P = 0.26). The area of CNV and subretinal fibrous tissue/disciform scar remained stable over time in both groups. The macular thickness significantly decreased through the follow-up period in both groups. The hyper-reflective area of the neovascular complex remained stable in both groups during the first 6 months of follow-up, whereas a slight increase of hyper-reflective lesion size occurred throughout the second 6 months of follow-up., Conclusion: The CNV lesion treated with IVB didn't disappear in neither group, but showed less exudation, demonstrated by a decrease in the area of leakage from CNV, subretinal fluid area, and centre point retinal thickness on OCT.

Purpose: To evaluate the circadian effects on intraocular pressure (IOP) and ocular perfusion pressure (OPP) of 0.5% timolol or 0.005% latanoprost in Caucasian patients affected by normal-tension glaucoma (NTG)., Patients and Methods: In this crossover trial, 30 consecutive NTG subjects underwent three 24-hour assessments of IOP, blood pressure (BP), heart rate (HR), and OPP [calculated according to the formula OPP = (1/3 systolic BP + 2/3 diastolic BP) x 2/3 - IOP]: at baseline, and after 1-month treatment with timolol or latanoprost. These parameters were recorded at 4 a.m., 8 a.m., noon, 4 p.m., 8 p.m., and midnight., Results: Both timolol and latanoprost reduced IOP (p < 0.001), with a difference in favour of latanoprost of 1.3 mmHg (95% CI 0.9, 1.6; p < 0.001). After timolol, BP and HR decreased with respect to baseline (p < 0.001). Latanoprost increased mean OPP (3.6 mmHg, 95% CI 2.9, 4.3; p < 0.001), whereas timolol did not improve it., Conclusions: Latanoprost induces an IOP reduction greater than timolol, also achieving a better circadian flattening of the IOP curve. Only latanoprost significantly increased mean 24-hour OPP. The management of Caucasian NTG patients should be critically realized, considering the 24-hour influence of each IOP-lowering drug on the ocular blood perfusion.

Purpose: To assess the efficacy and side effects of 0.005% latanoprost once daily during 3 years of treatment in glaucomatous patients in whom intraocular pressure (IOP) was not adequately controlled by beta-blockers twice daily., Methods: An unmasked prospective study was performed on 76 glaucomatous patients (145 eyes) treated with 0.005% latanoprost at bedtime, after a 21-day wash-out period from beta-blockers. IOP measurement and visual field examination were recorded over the follow-up period., Results: Latanoprost significantly reduced IOP from 26.5+/-6.6 mmHg (mean +/- SD) to 17.4+/-2.7 mmHg after 36 months of treatment in 48 patients (63.1%), who completed the trial. Twenty-eight patients (36.8%) discontinued the therapy. In 12 patients (15.8%) the treatment did not obtain a satisfactory target IOP. In two subjects (2.6%), despite the IOP reduction, visual field damage progressed. The remaining 10 patients (13.1%) discontinued the treatment because of the following side effects: microfollicular conjunctivitis (seven cases); severe oedema of conjunctiva and eyelids (one case); corneal punctate erosion (one case); cystoid macular oedema (one case). No flare or pigmentary changes of iris and eyelash were observed., Conclusion: Latanoprost 0.005% once daily significantly reduces IOP in the majority of glaucomatous patients uncontrolled by beta-blockers. The reduction of IOP was statistically significant during 3 years of follow-up, confirming the clinical efficacy of this compound. The ocular side effects requiring cessation of therapy were mainly allergic reactions. The most severe adverse effects were one case of corneal punctate erosion and one case of cystoid macular oedema in a pseudophakic patient.

Background: This study evaluated the conjunctival effects of latanoprost and timolol, both of which contain benzalkonium chloride, in patients with primary open-angle glaucoma (POAG), with and without a history of allergic conjunctivitis (AC)., Methods: Two groups of 25 patients with and without a positive history for AC were studied. After a 21-day wash-out period patients were randomized to 14 days treatment with latanoprost or with timolol, in a cross-over fashion. The following parameters were evaluated on days 0 and 14: number of white blood cells, ferning test, conjunctival impression cytology, subjective symptoms, and objective ocular changes., Results: Latanoprost caused: (a) an increase in eosinophils in both groups and reduction in lymphocytes only in the group with a history of AC; (b) alterations in ferning test and impression cytology only in AC patients; and (c) development of subjective symptoms and objective signs only in non-AC glaucomatous subjects. Timolol therapy was responsible only for the occurrence of subjective symptoms and objective signs in non-AC patients., Conclusion: Latanoprost treatment induces ocular surface changes which are more evident in POAG patients who are also affected by AC. These findings are probably related to the very high latanoprost concentration of benzalkonium chloride and to its bedtime administration, which further amplifies the toxicity.

Purpose: To examine the relation between perfusion of the optic nerve head and visual field defects in glaucomatous patients., Methods: A study was performed on 94 patients affected with primary open-angle glaucoma. The optic nerve head blood flow was measured by means of a scanning laser Doppler flowmeter (Heidelberg Retina Flowmeter). Blood volume, flow and velocity were analysed in two areas of the rim and in one area of the lamina cribrosa. The visual field was tested with the 30-2 full threshold white-on-white program and mean deviation (MD) and corrected pattern standard deviation (CPSD) were considered as parameters of visual field defects., Results: The interindividual analysis showed that the vascular parameters of the neuroretinal rim circulation were not significantly correlated with visual field parameters. The blood volume, flow and velocity of lamina cribrosa correlated significantly with both MD (R=0.519, R=0.549 and R=0.531, respectively; P<0.001) and CPSD (R=-0.496, R=-0.363 and R=-0.363, respectively; P<0.001). The intraindividual correlations (right-left differences of parameters) showed that the side differences of MD and CPSD correlated significantly with the side differences of blood volume (R=0.511 and R=-0.477, respectively), flow (R=0.554 and R=-0.390, respectively) and velocity (R=0.541 and R=-0.372, respectively) in lamina cribrosa., Conclusion: These findings suggest that in glaucoma patients the perfusion parameters of lamina cribrosa are significantly correlated with visual field defects.

Background: Several inherited conditions have been associated with an increased or decreased incidence of retinal vein occlusion (RVO). The A allele in the 20210 G/A prothrombin gene has been found to be associated with systemic venous thrombosis. The aim of this study has been to verify the prevalence of this mutation in patients affected by central RVO (CRVO) or branch RVO (BRVO)., Methods: A retrospective study was carried out on 100 consecutive patients suffering from RVO, more than 50 years old, unaffected by systemic diseases known to be associated with markedly increased RVO occurrence. We determined the frequency of this mutation by performing mutagenised amplification of exon 14 followed by restriction analysis of the amplified DNA fragment., Results: The overall frequency of prothrombin 20210A allele in RVO patients was 6.0%. All heterozygous patients had suffered from CRVO. In this study subgroup, the frequency of the 20210 G/A prothrombin heterozygosis was 12.0%. The difference in the frequency of this the genetic variant between the CRVO and BRVO groups was statistically significant. None of the conventional RVO risk factors were statistically related to the occurrence of the disease in either the CRVO or the BRVO subgroup., Conclusion: The prevalence of the prothrombin 20210A mutation observed in CRVO patients is significantly higher than in the normal Italian population. Moreover, the prevalence is significantly greater in CRVO than in BRVO patients. These results raise the possibility that the prothrombin 20210A variant may be considered as a risk factor for CRVO.

Background: Ketanserin is a specific antagonist of 5-HT2 and 5-HT1c receptors. These receptors are linked to the stimulation of phosphoinositide metabolism and are involved in IOP controls. Orally and topically administered ketanserin reduces IOP in normotensive and glaucomatous eyes., Methods: Ketanserin 0.5% eye drops were administered to 20 patients with primary open-angle glaucoma in a randomised, crossover, double-masked fashion to evaluate the effect of ketanserin in glaucomatous patients already receiving timolol who did not have controlled IOP (> 21 mmHg). Mean and range of IOP curve (8.00 a.m.-8.00 p.m.), pupil diameter, Schirmer I, basal secretion test and BUT values were recorded at baseline and after 2 weeks of topical administration of ketanserin or placebo twice daily. The alternative treatment was given 2 weeks later and the same protocol was repeated., Results: When patients received placebo no significant variations were found in the analysed parameters. Ketanserin significantly reduced mean IOP (19.5%) and was effective for up to 12 h without inducing variations of tear secretion or pupil diameter. No systemic side effects were observed, and no significant variations in ocular symptoms and signs were reported., Conclusion: These results indicate that topical administration of ketanserin may be useful to reduce IOP in patients not controlled with beta-blockers.