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Introduction: Iris retraction syndrome (IRS) is a rare clinical condition characterized by a backbowing of the iris positioned on the lens with a complete pupillary block. Immune checkpoint inhibitors (ICIs) are a new class of immunomodulating agents used in cancer therapy, and although they have high response rates, ophthalmic-related side effects have been reported. We report a rare case of bilateral IRS with hypotony after therapy with nivolumab. Case Presentation: We present a case of bilateral IRS with hypotony, 3 mm Hg OD and 5 mm Hg OS, after therapy with nivolumab. The patient presented with decreased vision, corneal edema, keratic precipitates, deep anterior chamber with posterior synechiae, and hypotony maculopathy. Anterior segment OCT revealed a sharp posterior displacement of the iridolenticular diaphragm consistent with IRS. Discontinuation of nivolumab until ocular improvement was suggested, following oncologic consultation. Four months later, the patient exhibited iris bombé with angle closure and increased IOP. This was managed with phacoemulsification and concomitant surgical iridectomy. One month after surgery, the patient's IOP had returned to physiologic values, and the iris configuration had returned to normal. Conclusion: The exact mechanism of IRS remains unclear, but it is suggested that an aqueous imbalance, in conjunction with uveitis and hypotony, creates an anterio-posterior movement of the iridolenticular diaphragm when the pupillary block is present. Our case highlights the importance of monitoring patients receiving ICIs for ophthalmic adverse effects and prompt management to prevent permanent visual damage. In conclusion, this is the first reported case of IRS after therapy with ICIs. Further research is needed to fully understand the exact mechanism by which it is induced.
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Purpose: To present a case involving a rarely seen prototype posterior chamber phakic IOL (PC-pIOL) in a highly myopic patient with bilateral cataract. Observations: A 64-year-old male presented to our clinic with poor vision in both eyes. Clinical examination revealed bilateral mature cataract, phacodonesis as well as a PC-pIOL implanted 35 years ago to address his high myopia. The visual acuity (VA) was 20/200 in the right eye and no light perception in the left eye. PC-pIOL extraction as well as 23G pars plana vitrectomy (PPV) and fragmentation surgery was scheduled for the right eye. The left eye was treated conservatively. Successful extraction of the PC-pIOL was performed while it was easy to remove. It was a bow-tie shaped lens with a collar-stud-like button in the middle which extended anteriorly into the anterior chamber through the pupil. PPV with lens fragmentation was successful and the patient was left aphakic in order to avoid the placement of a zero diopter IOL. Final best corrected VA was 20/25 one month post-surgery. Conclusions and importance: Removal of this rarely seen pIOL was performed without difficulty while excellent VA was achieved. Aphakia following complete vitrectomy represented a viable option in this case. Furthermore, we highlight the clinical manifestations associated with this IOL more than three decades after implantation.
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Selective screening for inherited metabolic disorders (IMD) began in Cyprus in 1990. Over the last thirty-three years 7388 patients were investigated for IMD and 200 diagnoses were made (diagnostic yield 2.7%). The existence of a single laboratory of Biochemical Genetics for the whole island facilitated the creation of a national registry for IMD. The minimal prevalence of IMD in Cyprus is 53.3 cases per 100,000 live births. The most common group are disorders of amino acid metabolism (41.0%), followed by disorders of carbohydrate metabolism (16.5%), disorders of complex molecule degradation (16.5%), mitochondrial disorders (10.5%) and disorders of vitamin and co-factor metabolism (5.5%). Hyperphenylalaninaemia is the most common IMD (14.0%) followed by galactosaemia (7.0%), glutaric aciduria type I (5.5%) and MSUD (4.0%). Some disorders were found to have a relatively high incidence in specific communities, for example Sandhoff disease among the Cypriot Maronites and GM1 gangliosidosis in one particular area of the island. Other disorders were found to have a relatively higher overall incidence, compared to other Caucasian populations, for example galactosaemia, glutaric aciduria type I and MSUD, while fatty acid oxidation defects, Gaucher disease and classic PKU were found to have a relatively lower incidence. Molecular characterization of selected disorders revealed many novel genetic variants, specific to the Cypriot population.
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Aim: To present a complex case of Ahmed tube exposure 6 months after the implantation associated with corneal melting and iris prolapse, and the surgical reposition that required multiple allografts and limbal reconstruction. Methods: A 60-year-old patient arrived at the emergency room with tube exposure combined with corneal melting and iris prolapse from a previously placed Ahmed valve 6 months prior. Our approach was to use one corneoscleral graft to repair the melted cornea and avoid further iris prolapse and a second scleral graft to cover the repositioned tube. Upon completion of conjunctival dissection, cleaning and deepithelization of the melted cornea and the tube by application of alcohol 100% followed. A new entry point was made for the tube and was covered using an alcohol-preserved scleral allograft and the previous entry point was repaired using a corneoscleral allograft with the corneal aspect restoring the limbus and avoiding further iris protrusion. Results: 6 months follow-up of the patient showed excellent recovery, anatomical restoration, and IOP normalization. Conclusion: Surgical repair of these cases can be very demanding, and requires surgical improvisation and prolonged surgical time. The literature remains very limited on how a surgeon should approach similar cases, which are the crucial tips, and which are the missteps that should be avoided. In this case, we used multiple scleral/corneoscleral allografts in a specific orientation and different sutures to reconstruct the damaged limbal area and restore the anatomy. Abbreviations: VA = Visual Acuity, GDD = Glaucoma Drainage Device, IOP = Intra Ocular Pressure.
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Úlcera de la Córnea , Glaucoma , Humanos , Persona de Mediana Edad , Glaucoma/complicaciones , Glaucoma/diagnóstico , Córnea , Iris , Etanol , AloinjertosRESUMEN
BACKGROUND: Dihydropyrimidine dehydrogenase (DPD), is the initial and rate-limiting enzyme in the catabolic pathway of pyrimidines. Deleterious variants in the DPYD gene cause DPD deficiency, a rare autosomal recessive disorder. The clinical spectrum of affected individuals is wide ranging from asymptomatic to severely affected patients presenting with intellectual disability, motor retardation, developmental delay and seizures. DPD is also important as the main enzyme in the catabolism of 5-fluorouracil (5-FU) which is extensively used as a chemotherapeutic agent. Even in the absence of clinical symptoms, individuals with either complete or partial DPD deficiency face a high risk of severe and even fatal fluoropyrimidine-associated toxicity. The identification of causative genetic variants in DPYD is therefore gaining increasing attention due to their potential use as predictive markers of fluoropyrimidine toxicity. METHODS: A male infant patient displaying biochemical features of DPD deficiency was investigated by clinical exome sequencing. Bioinformatics tools were used for data analysis and results were confirmed by MLPA and Sanger sequencing. RESULTS: A novel intragenic deletion of 71.2 kb in the DPYD gene was identified in homozygosity. The deletion, DPYD(NM_000110.4):c.850 + 23455_1128 + 8811del, eliminates exons 9 and 10 and may have resulted from a non-homologous end-joining event, as suggested by in silico analysis. CONCLUSIONS: The study expands the spectrum of DPYD variants associated with DPD deficiency. Furthermore, it raises the concern that patients at risk for fluoropyrimidine toxicity due to DPYD deletions could be missed during pre-treatment genetic testing for the currently recommended single nucleotide polymorphisms.
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Deficiencia de Dihidropirimidina Deshidrogenasa , Lactante , Humanos , Masculino , Deficiencia de Dihidropirimidina Deshidrogenasa/genética , Deficiencia de Dihidropirimidina Deshidrogenasa/complicaciones , Deficiencia de Dihidropirimidina Deshidrogenasa/tratamiento farmacológico , Dihidrouracilo Deshidrogenasa (NADP)/genética , Dihidrouracilo Deshidrogenasa (NADP)/metabolismo , Antimetabolitos Antineoplásicos/efectos adversos , Fluorouracilo/efectos adversos , Pruebas GenéticasRESUMEN
We conducted a systematic review and meta-analysis to assess the association between optical coherence tomography angiography (OCTA) parameters and acute coronary syndrome (ACS). Two independent reviewers searched the electronic databases (MEDLINE (Medical Literature Analysis and Retrieval System Online), Scopus, Embase (Excerpta Medica Database), Cochrane Library, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform) from inception until April 2023. According to the inclusion criteria of this review, eligible were observational studies, randomized control trials, and registry/database studies that included the eyes of adult ACS patients and assessed OCTA parameters within the macula. The pooled standardized mean differences (SMD) between patients diagnosed with ACS and healthy controls with a confidence interval (CI) of 95% were calculated using the Hartung-Knapp-Sidik-Jonkman random-effects method. The heterogeneity was assessed by I2 and the Cochran Q and a random effects model was applied. Seven studies were eligible and included in our systematic review (n = 898), of which three were included in the meta-analysis (n = 341). The pooled SMD in the superficial vascular plexus (SVP), deep vascular plexus (DVP), and foveal avascular zone (FAZ) were -0.46 (95% CI: -0.94 to 0.01, p = 0.05, I2 = 0%, three studies), -0.10 (95% CI: -3.20 to 3.00, p = 0.75, I2 = 67%, two studies), and 0.43 (95% CI: -1.22 to 2.09, p = 0.38, I2 = 92%, three studies), respectively. Our findings suggest that there are no differences in OCTA metrics between ACS patients and healthy individuals.
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OBJECTIVE: To examine the use of Carlevale IOL placement in patients with UGH, and to evaluate surgical outcomes. DESIGN: In this retrospective study, 28 patients with UGH syndrome that were subjected to IOL explantation and concomitant Carlevale IOL implantation were included in the study. METHODS: Information about VA, IOP, number of glaucoma medication, need for glaucoma surgery, presence of hemorrhage and inflammation were recorded up to 6 months after the procedure. RESULTS: We found a statistically significant increase in mean visual acuity and complete resolution of uveitis in all patients. Mean IOP and the mean number of glaucoma medications were significantly decreased postoperatively, while 14% of patients required additional glaucoma surgery. CONCLUSIONS: IOL explantation and concomitant Carlevale IOL implantation may provide a viable solution for UGH syndrome resolution, increases visual acuity, and decreases the need for glaucoma medication.
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Glaucoma de Ángulo Abierto , Glaucoma , Lentes Intraoculares , Uveítis , Humanos , Estudios Retrospectivos , Glaucoma de Ángulo Abierto/cirugía , Glaucoma/cirugía , Glaucoma/etiología , Procedimientos Quirúrgicos Oftalmológicos , Hipema , Uveítis/cirugía , Uveítis/etiología , Complicaciones Posoperatorias/etiología , Lentes Intraoculares/efectos adversosRESUMEN
Objectives: Our aim was to perform a perfluorobutylpentane (F4H5) washout in conjunction with glaucoma drainage device (GDD) placement in patients with silicone oil (SO)-induced glaucoma. In this report we present our preliminary results concerning the effectiveness in clearing the SO and the safety of the procedure. Materials and Methods: Eight patients who previously underwent pars plana vitrectomy with SO tamponade due to retinal detachment were selected. Removal of SO was performed on average 10 months after initial surgery. All patients developed glaucoma with evidence of SO remnants in the anterior chamber (AC) and angle. Removal of the remaining SO with F4H5 washout was performed in all cases with concomitant insertion of a GDD to treat the refractory glaucoma. Intraocular pressure (IOP), SO remnants, endothelial cell count, and need for glaucoma medications were evaluated up to 12 months after the surgical procedure. Results: All patients had uneventful surgery with no major complications 12 months postoperatively. A marked reduction of SO remnants in the AC and angle was observed in all cases after surgery. There was a 60.9% decrease in mean IOP 12 months postoperatively (p<0.05) and the need for glaucoma medication was lower in all patients (mean topical medicines: 4 preoperatively vs. 0.75±0.89 postoperatively; p<0.05). Endothelial cell density showed no significant change (mean 2012±129 cells/mm2 preoperatively vs. 1985±134 cells/mm2 postoperatively; p>0.05), and there were no signs of corneal edema. Conclusion: F4H5 is an effective emulsifier for removing SO remnants and may be safely used in conjunction with GDD placement in order to control IOP in eyes with silicone oil-induced glaucoma.
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Implantes de Drenaje de Glaucoma , Glaucoma , Humanos , Aceites de Silicona , Proyectos Piloto , Glaucoma/etiología , Implantes de Drenaje de Glaucoma/efectos adversosRESUMEN
Pompe disease is a rare metabolic myopathy caused by pathogenic variants affecting the activity of the lysosomal glycogen-degrading enzyme acid alpha-glucosidase (GAA). Impaired GAA function results in the accumulation of undegraded glycogen within lysosomes in multiple tissues but predominantly affects the skeletal, smooth and cardiac muscle. The degree of residual enzymatic activity appears to roughly correlate with the age of onset and the severity of the clinical symptoms. Here, we report four siblings in which the GAA variants NM_000152.5:c.2237G > C p.(Trp746Ser) and NM_000152.5:c.266G > A p.(Arg89His) were identified as an incidental finding of clinical exome sequencing. These variants are listed in the ClinVar and the Pompe disease GAA variant databases but are reported here for the first time in compound heterozygosity. All four siblings displayed normal urine tetrasaccharide levels and no clinical manifestations related to Pompe disease. Nevertheless, GAA enzymatic activity was within the range for late onset Pompe patients. Our report shows an association between a novel genotype and attenuated GAA enzymatic activity. The clinical significance can only be established by the regular monitoring of these individuals. The study highlights the major challenges for clinical care arising from incidental findings of next generation sequencing.
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Purpose: To investigate the morphological and functional correlation between microvascular retinal changes in optical coherence tomography angiography (OCTA) and the microvascular coronary circulation in patients with ST elevation myocardial infarction (STEMI) coronary heart disease (CHD). Methods: A total of 330 eyes from 165 participants (88 cases and 77 controls) were enrolled and imaged. Superficial capillary plexus (SCP) and deep capillary plexus (DCP) vascular density was measured in the central (1 mm) and perifoveal (1-3 mm) areas and in the superficial foveal avascular zone (FAZ) and choriocapillaris (3 mm). These parameters were then correlated to the left ventricular ejection fraction (LVEF), and the number of affected coronary arteries. Results: Decreased vessel densities in the SCP and DCP and choriocapillaris were positively correlated to the LVEF values (P = 0.006, P = 0.026, and P = 0.002, respectively). No statistically significant correlation between the SCP and DCP central area or FAZ area was found. Regarding the number of affected vessels, significant negative correlations were revealed for the SCP and DCP central vessel densities (P < 0.001 and P < 0.001, respectively) and the SCP perifoveal vascular density (P = 0.009). Conclusions: OCTA vascular indices are significantly correlated with morphological and functional parameters in patients with STEMI CHD. SCP vascular density especially seems to be a promising biomarker for the extent of both macrovascular damage (number of affected coronary arteries) and microvascular damage, as mirrored in the decreased LVEF at admission. Translational Relevance: OCTA vascular indices offer a valuable insight into the microvascular status of coronary circulation.
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Infarto del Miocardio con Elevación del ST , Humanos , Infarto del Miocardio con Elevación del ST/diagnóstico por imagen , Vasos Retinianos/diagnóstico por imagen , Angiografía con Fluoresceína/métodos , Volumen Sistólico , Fondo de Ojo , Función Ventricular IzquierdaRESUMEN
Silicone oil (SO) has been widely used as intravitreal tamponade agent for rhegmatogenous retinal detachment (RRD) and has been occasionally associated with incomplete retinal structural and functional recovery. The use of Optical Coherence Tomography Angiography (OCT-A) has recently attracted significant attention for detailed analysis of retinal capillary plexus and blood flow changes as predicting factors for postoperative outcomes. A detailed literature search was performed in PubMed database until October 2022. The following keywords were used: rhegmatogenous retinal detachment, silicone oil, optical coherence tomography angiography, macular microvasculature, peripapillary capillary plexus, vessel density, and foveal avascular zone. We identified and reviewed 19 studies referring to microcirculation alterations of the retinal capillary plexus as seen on OCT-A in eyes treated by vitrectomy with intravitreal SO for RRD. A comprehensive update revealed variability of microcirculation characteristics of the retinal capillary plexus including the macular and the peripapillary capillaries. Further studies are warranted to clarify the OCT-A values in an attempt to identify the potential effect of SO on retinal tissue in clinical practice. A review of the existing literature sheds light on the effect of SO on retinal capillary plexus and the potential impact on functional outcomes after vitrectomy for RRD. This article discusses important aspects of key publications on the topic, highlights the importance to identify distinct alterations of the microvasculature status, and proposes the need for further future research in this field.
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Corneal endothelium is a single cell layer that is mainly responsible for maintaining corneal clarity. Endothelial damage secondary to toxicity, stress, or genetic predisposition are common and in conjunction with the low regenerative ability of the cells, making their preservation critical for maintaining visual acuity. Patients with glaucoma, who are estimated to be close to 80 million worldwide, have a plethora of reasons for developing endothelial damage, being exposed to a spectrum that extends from various medical and surgical interventions to the disease itself. The wide spectrum of glaucoma pharmacotherapy that has been recently extended by addition of newer classes of medications has been the focus of extensive research on its effects on corneal endothelium. Both basic and clinical research have attempted to shine a light on the complex mechanisms associated with the effects of glaucoma medication on corneal endothelium and to answer the important question as to whether these findings are clinically significant. The aim of this review is to summarize and present current literature of the various findings, both from in vivo and in vitro studies that have focused on the complex relationship between different classes of glaucoma medication and their effect on corneal endothelium.
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PURPOSE: To investigate correlations of exophthalmometry values (EVs) with age, gender, and the presence of diabetes mellitus, arterial hypertension, and dyslipidemia. METHODS: In a cross-sectional, clinic-based study, consecutive adult Greek patients presenting for evaluation at the outpatient general clinic on a scheduled appointment basis at a tertiary care referral center were submitted to Hertel exophthalmometry in both eyes by the same observer. Subjects with signs of history or orbital pathology, including thyroid-associated ophthalmopathy, were excluded. Demographics, as well as a detailed systemic history report, were recorded. Mixed effect linear regression analysis was performed to account for the correlation between the eyes of the same participant. RESULTS: A total of 800 eyes (400 subjects) were included, 194 males and 206 females, with a mean age of 67.82 ± 12 years (range: 18-92 years). The mean exophthalmometry value was 15.7 ± 2.6 mm (range: 11-21 mm). Every one year of increase in age is associated with a decrease in EVs by 0.03 mm (95% CI -0.04, -0.02/p-value<0.001). Female gender was associated with lower EVs by 0.33mm (95% CI-0.56, -0.1/p-value=0.005). Patients with diabetes mellitus had higher EVs by 0.47 mm (95% CI 0.25, 0.70/p-value<0.001) compared to patients without diabetes, and patients with arterial hypertension had lower EVs by 0.26 mm (95% CI -0.5, -0.02/p-value=0.034) compared to patients without hypertension. No association was found between dyslipidemia and systemic history of thyroid dysfunction. Conclusions: A negative correlation of EVs was noted with increasing age, female gender, as well as history of arterial hypertension and a positive correlation with diabetes mellitus.
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A 39-year-old woman, without any systemic or ocular history, presented with a paracentral scotoma in her right eye with normal visual acuity. Humphrey's visual fields showed a reversible enlargement of the right blind spot. The final diagnosis was acute idiopathic blind spot enlargement which was successfully treated with intravenous steroids. Although differential diagnosis of blind spot enlargement can be challenging, multimodal imaging with combination of visual field's assessment can help us make the right diagnosis.
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BACKGROUND: To examine the association between optical coherence tomography angiography (OCTA) retinal measurements and Parkinson's disease (PD). METHODS: We searched MEDLINE and EMBASE from inception up to November 5th, 2021 for studies examining the differences between OCTA retinal measurements in PD patients and healthy controls. We used the Hartung-Knapp-Sidik-Jonkman random-effects method to combine study-specific standardized mean differences (SMD) in pooled effect estimates and a meta-analytic extension of the E-value metric to quantify the confounding bias capable of nullifying the pooled estimates. RESULTS: Nine eligible studies for our systematic review were identified through our search strategy. The pooled SMD between the retinal vessel density of PD patients and healthy participants in the whole superficial vascular plexus (SVP), foveal SVP, parafoveal SVP and foveal avascular zone (FAZ) was -0.68 (95% CI: -1.18 to -0.17, p value = 0.02, n = 7 studies), -0.14 (95% CI: -0.88 to 0.59, p value = 0.62, n = 5 studies), -0.59 (95% CI: -1.41 to 0.23, p value = 0.12, n = 5 studies) and -0.20 (95% CI: -0.79 to 0.38, p value = 0.39, n = 5 studies), respectively. An unmeasured confounder would need to be associated with a 3.01-fold, 1.54-fold, 2.81-fold and 1.70-fold increase in the risk of PD and OCTA retinal measurements, in order for the pooled SMD estimate of vessel density in whole SVP, parafoveal SVP and FAZ, respectively, to be nullified. CONCLUSIONS: Our results provide evidence on an inverse association between whole SVP vessel density and PD.
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Enfermedad de Parkinson , Tomografía de Coherencia Óptica , Humanos , Angiografía con Fluoresceína/métodos , Tomografía de Coherencia Óptica/métodos , Enfermedad de Parkinson/diagnóstico por imagen , Fondo de Ojo , Vasos Retinianos/diagnóstico por imagen , Fóvea Central/irrigación sanguíneaRESUMEN
Background and objectives: We aimed to evaluate the effects of the water drinking test (WDT) on several systemic and ocular parameters, including choroidal thickness, which was assessed through optical coherence tomography angiography (OCTA), in glaucoma suspects. Materials and Methods: A total of 40 eyes from 20 glaucoma suspects without any systemic or ocular diseases were included in this prospective observational study. All the participants undertook the WDT, which required the drinking of 1 L of table water in 5 min. The outcome measures included IOP, systolic and diastolic blood pressure (SBP and DBP), mean arterial pressure (MAP), mean ocular perfusion pressure (MOPP), ocular pulse amplitude (OPA), and subfoveal and peripapillary choroidal thickness, which were assessed at baseline and at four 15 min intervals after the WDT. Generalized least squares models and mixed model analyses that take into account repeated measurements were used to assess the changes over time of these parameters. Results: All the ocular and systemic parameters showed statistically significant changes at all time points compared to baseline apart from choroidal thickness. The peak changes were an IOP of 20.1 mmHg versus 17.3 mmHg at 45 min, an SBP of 137.6 mmHg versus 125 mmHg at 30 min, a DBP of 95.9 mmHg versus 85.7 mmHg at 15 min, and an MOP of 53.51 mmHg versus 48.89 mmHg at 15 min. Conclusions: Despite elevations in IOP and significant changes in all the assessed systemic parameters, the WDT was not associated with changes in choroidal thickness in glaucoma suspects.
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Glaucoma de Ángulo Abierto , Presión Intraocular , Humanos , Tonometría Ocular , Coroides , Agua , Tomografía de Coherencia ÓpticaRESUMEN
To describe an in-office minimal approach technique for closing recently operated full thickness macular holes (FTMH), when closure was not fully achieved or there was macular hole re-formation, without performing another pars plana vitrectomy (PPV). Retrospective case series study. Nine patients were included in this case series. All patients were diagnosed with FTMH characterized by a decrease in visual acuity (VA) and metamorphopsias. All patients initially underwent a standard PPV procedure with 20% sulfur hexafluoride (SF6) injection. After 1-16 weeks, no closure or reformation of the macular hole was observed. Fluid-SF6 exchange was performed in the slit lamp, with the aim of injecting a 50% gas bubble of pure SF6 into the vitreous cavity, according to a minimally invasive in-office technique. Postoperatively, all patients achieved successful macular hole closure and VA showed an average improvement of approximately 4 lines on the EDTRS logarithm of the minimum angle of resolution (logMAR) chart. In particular, the mean corrected distance visual acuity improved from 0.99 ± 0.27 logMAR to 0.33 ± 0.23 logMAR (P = 0.03). The minimal surgical in-office technique of SF6 injection for the management of reopened macular holes after a recent PPV procedure shows promising results.
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Perforaciones de la Retina , Humanos , Perforaciones de la Retina/cirugía , Perforaciones de la Retina/diagnóstico , Hexafluoruro de Azufre , Estudios Retrospectivos , Vitrectomía/métodos , Agudeza VisualRESUMEN
PURPOSE: To present a case of branch retinal vein occlusion (BRVO) following ChAdOx1 nCoV-19 (Oxford-AstraZeneca) Vaccine. METHODS: Case report. RESULTS: A 60-year old otherwise healthy Caucasian male, presented to the ophthalmology emergency clinic complaining of sudden, painless vision loss in his right eye of 24 h" duration. The patient had received Vaxveria seven days prior. The clinical and fundus examination of the right eye established the diagnosis of BRVO. CONCLUSION: The present case descibes the occurrence of BRVO soon after the vaccination with the Oxford-AstraZeneca vaccine. The close temporal relationship between the BRVO incidence and the vaccination is reinforced by the lack of othe subjective cause to justify the episode.