Quantitative Parameters Relevant for Diabetic Macular Edema Evaluation by Optical Coherence Tomography Angiography.

Diabetic macular edema (DME) is one of the main ocular complications of diabetes mellitus (DM) that can lead to important vision loss in diabetic patients. In clinical practice, there are cases of DME with unsatisfying treatment responses, despite adequate therapeutic management. Diabetic macular ischemia (DMI) is one of the causes suggested to be associated with the persistence of fluid accumulation. Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality, able to give in-depth information about retinal vascularization in a 3-dimensional manner. The OCTA devices currently available can provide various OCTA metrics that quantitatively assess the retinal microvasculature. In this paper, we reviewed the results of multiple studies that investigated the changes in OCTA metrics in the setting of DME and their possible contribution to the diagnosis, therapeutic management, follow-up and prognosis of patients with DME. We analyzed and compared relevant studies that investigated OCTA parameters related to changes in macular perfusion in the setting of DME and we evaluated the correlations between DME and several quantitative parameters, such as vessel density (VD), perfusion density (PD), foveal avascular zone (FAZ)-related parameters, as well as complexity indices of retinal vasculature. The results of our research showed that OCTA metrics, evaluated especially at the level of the deep vascular plexus (DVP), are useful instruments that can contribute to the assessment of patients with DME.

Retromode Imaging in Age-Related Macular Degeneration.

Background and Objectives: Retromode is a relatively new retinal-imaging technique that is based on the transillumination principle and is obtained with a scanning laser ophthalmoscope that uses light in the infrared spectrum. The laser light penetrates into the deep retinal layers and the choroid. Retromode images are captured with a laterally displaced aperture, and the detector captures only the scattered light. The result is a high-contrast pseudo-three-dimensional image. Age-related macular degeneration (AMD) is a disabling retinal disease. AMD is characterized in its early stage by small and intermediate drusen formation, while the signs of intermediate AMD are large drusen and/or pigmentary abnormalities. Late AMD has two forms, geographic atrophy, which is the advanced form of dry AMD, and wet AMD. Most of the lesions of AMD are located in the outer layers of the retina. This new imaging method can provide a glimpse of the deep retinal layers' topographic changes in a non-invasive, fast, and effective way that can match the other imaging tools available. Materials and Methods: The literature review was performed by searching the PubMed database using the following combination of keywords: retromode imaging and age-related macular degeneration. Relevant images similar to the ones in the literature were identified and used as models. Results: The purpose of this article is to highlight the utility of incorporating retromode imaging into the multimodal evaluation of the retina in patients with AMD and to gather and integrate these findings into a brief but comprehensive paper. Conclusions: Retromode imaging is a good screening, diagnosis, and monitoring tool for patients with AMD.

Highlights on Genetic Polymorphism Associated with Thromboembolic Risk; Implications in Ophthalmic and Autoimmune Disorders-A Review.

The present paper explores genetic polymorphism and its association with thromboembolic retinal venous disorders, such as central/hemi-retinal vein occlusion, as well as possible correlations with other ocular findings, such as closed angle glaucoma, but also with autoimmune general disorders. In this review, we are highlighting the importance of establishing a correspondence between all of the above, since they all have complex etiopathogeneses; sometimes, when all coexist together, they could generate effects that may be very difficult to manage. There are studies supporting that genetic polymorphism, such as the variant MTHFR A1298C, may increase the risk for developing glaucoma, especially in the heterozygote model. Being aware of all these aspects may prove to be useful in patients with several associated diseases, as a combined effort between several medical specialties may prove to the benefit of these patients. Our review, completed with an exemplifying clinical case, shows that it is necessary to raise awareness of all aspects of a complex medical situation, including the genetic one, of a patient being at risk for thromboembolic episodes, for preventing them or managing them promptly and properly in the future.

Erratum: [Corrigendum] Corneal endothelial changes induced by pars plana vitrectomy with silicone oil tamponade for retinal detachment.

[This corrects the article DOI: 10.3892/etm.2021.10393.].

Corneal endothelial changes induced by pars plana vitrectomy with silicone oil tamponade for retinal detachment.

Silicone oils are effective intraocular tamponade agents in the treatment of severe retinal detachments, because they maintain the adhesion between neurosensory retina and retinal pigment epithelium, thanks to their ability to remove aqueous humor from the surface of the retina. To understand their effectiveness, it is important to know the characteristics of silicone oils. Patients should be closely monitored due to many complications associated with intraocular silicon oil, such as inflammatory reaction, raised intraocular pressure, refraction disorders, cataract, and emulsification. This study presents corneal endothelial changes and some intraocular complications caused by silicone oil used as an intraocular tamponade agent in the case of vitrectomy for complex retinal detachments. The aim of the study was to demonstrate the damage of corneal endothelial cells after the use of silicone oil in patients with retinal detachment surgery. Endothelial specular microscopy measurements were performed and the changes of the following parameters demonstrated the corneal damage: Mean cell density, coefficient of variation, average cell area, percentage of hexagonal cells, and corneal thickness. Three months postoperatively, a statistically significant decrease was observed in the following analyzed parameters: Mean cell density (P=0.04), and percentage of hexagonal cells (P=0.002); the remaining parameters also had a linear decrease (coefficient of variation, average cell area), but were statistically insignificant. Three months postoperatively, the corneal thickness presented a slight increase. Silicone oils are powerful tools when used wisely and within the limits of their use. These are often recommended in cases of severe detachment of the retina in patients at high risk of experiencing intraoperative complications.

Endothelial corneal cell damage after pars plana vitrectomy: analogy of different intraocular tamponade agents.

A reduction in the corneal endothelial cells multitude after anterior pole intervention is well established in numerous researches, but there are few articles that follow the impact of vitreoretinal interventions on the cornea, especially when endotamponade agents are used. The assessment of the endothelial corneal cells is needed since it facilitates the personal evaluation of the functional endothelial stock. Specular microscopy investigation offers a scale of the functional strength of the endothelium of cornea, which is vital before all intraocular interventions. Endotamponade agents are very suitable and important tools in the surgical treatment of retinal detachment, but their use must be differentiated depending on the uniqueness of each patient. This research shows corneal endothelial damages caused by intraocular tamponade agents of different types in the case of pars plana vitrectomy for cases of multitude retinal detachments. The purpose of the research was to determine the changes that appear in the endothelium of the cornea and to deal with the results when different tamponade agents are used in the surgical cure for retinal detachment. Specular endothelial corneal microscopy records were achieved and the modifications of the following parameters revealed corneal implication: mean endothelial cell densities, average cell area, coefficient of variation, hexagonality and corneal center thickness. On the first day and at three months postoperatively, a statistically significant reduction was observed for the CV, MCD, and HEX parameters (p 0.001), but no statistically significant difference of the two endotamponade agents (for MCD, p=0.15; for CV, p=0.63; for HEX, p=0.93) was noticed. AVG parameter had a statistically significant decrease (p 0.001) and there was also a statistically significant difference of the two endotamponade agents (p=0.03), patients with gas tamponade presenting a superior result. On the first day and at three months postoperatively, the corneal center thickness presented a statistically significant increase (p 0.001) and there was a statistically significant difference between the two endotamponade agents (p=0.03), patients with gas endotamponade presenting a superior result. In conclusion, using the intraocular tamponade agents helps reestablish the functional-anatomical recovery of the retina after surgery, but their special indication must be well-established for each case of retinal detachment.

Comparative hematological profiles for dose-dense vs. regular anthracycline-based neoadjuvant chemotherapy in non-metastatic breast cancer.

The aim of the present study was to examine both the feasibility and toxicity of neoadjuvant dose-dense chemotherapy in women with non-metastatic breast cancer. A search within the OncoHelp Association breast cancer database has been performed in order to identify all non-metastatic breast cancer patients who underwent an initial consultation with a medical oncologist between March 2016 and April 2020. The inclusion criteria used were: i) Age, ii) follow-up care obtained at OncoHelp Association, iii) the intent to treat with a neoadjuvant dose-dense anthracycline every two weeks for four cycles (C1-C4) followed by paclitaxel every two weeks for four cycles, with white blood cell growth factor support, and iv) regular anthracycline-based chemotherapy every three weeks for four cycles, followed by paclitaxel every three weeks for four cycles, v) weight, vi) height, vii) Eastern Cooperative Oncology Group (ECOG) performance status, viii) hemoglobin (Hb) level, ix) Platelet count and x) neutrophil count.

Predictors of the response to nivolumab immunotherapy in the second or subsequent lines for metastatic non-small cell lung cancers.

Checkpoint inhibitors represent the first therapeutic class to replace chemotherapy lines for the treatment of metastatic non-small cell lung cancer (NSCLC), due to improved overall survival and tolerability. Nivolumab, a fully human anti-programmed cell death-1 immunoglobulin G4 monoclonal antibody, is the first immune checkpoint inhibitor approved by the US Food and Drug Administration in 2014 for cases of metastatic melanoma and in 2015 for cases of squamous cell lung cancer and kidney cell cancer. The present study aimed to identify predictive markers (favorable or unfavorable) for time to treatment discontinuation using nivolumab in the second or subsequent line of therapy of metastatic NSCLC cases. Analysis of a group of 78 NSCLC patients treated with nivolumab allowed the identification of negative predictive markers, related to the presence of metastases (adrenal in men under 65 years, liver, brain and the number of metastatic sites) and the hematological profile (neutrophilia at the initiation of treatment and lymphocyte variation at 6 weeks of treatment).

Vital dyes in macular hole surgery.

Currently, surgical techniques, such as internal limiting membrane peeling, are used widely for macular holes, macular puckers, epiretinal membranes, diabetic macular edema, retinal detachment, retinal vein occlusions, vitreomacular traction, optic pit maculopathy, and Terson syndrome. This study aimed to highlight any differences regarding visual acuity and ocular tomography coherence changes after staining the internal limiting membrane with dilutions of Brilliant Blue G vs. lutein/zeaxanthin-based dyes. This study involved 30 eyes of 30 patients who had undergone posterior pole vitrectomy for idiopathic stage 4 macular hole. The study lot was divided in two subgroups, 15 eyes colored with Brilliant Blue and the other 15 eyes colored with lutein and zeaxanthin dyes. The association between visual prognosis, ocular tomography coherence changes and intraocular pressure was analyzed. The surgical treatment with required endoillumination levels and a 2-min period of dye using the Alcon Constellation Vision System had no negative impact on cell viability and improved visual acuity by 30%. Staining makes it easier to remove, to be quick and precise while performing macular surgeries. In has been observed that lutein and zeaxanthin dyes offer an intraoperative protective screen that protects photoreceptors more than Brilliant Blue while performing pars plana vitrectomy. Both study groups had good results in time. Surgical visualization is an evolving technology.

Femtosecond-LASIK outcomes using the VisuMax®-MEL® 80 platform for hyperopia and hyperopic astigmatism refractive surgery.

The present study evaluated the efficacy, the safety and the predictability of the Femtosecond laser-assisted in situ keratomileusis (Femto-LASIK) procedure for hyperopia and hyperopic astigmatism. We retrospectively analyzed the postoperative 12-month evolution of 593 eyes with hyperopia and hyperopic astigmatism that underwent Femto-LASIK treatment. The procedure was predictable and effective. No eye lost 2 lines of corrected distance visual acuity (CDVA), demonstrating a safety profile of the procedure. Nine percent of the eyes gained at least one line of CDVA. The accuracy of the spherical equivalent after 12 months was 74% within ±1.0 diopter (D) of emmetropia. The refractive outcomes were stable during the follow-up period. There were no significant complications during the procedure. Femto-LASIK using the VisuMax®-MEL® 80 platform was demonstrated to be a suitable option to correct selected cases of hyperopia and hyperopic astigmatism. A longer follow-up period is required to better assess the refractive results and to detect any further regression.

Determining factors of renal dysfunction during cisplatin chemotherapy.

Cisplatin remains one of the most active antineoplastic treatments used in oncology, being the most prestigious exponent of the golden age in chemotherapy at the end of the 20th century. This chemotherapeutic drug is used for curative or palliative treatments in testicular, ovarian, head and neck neoplasms, sarcomas and lymphomas. The limiting dose adverse effect of cisplatin is nephrotoxicity. The present study aimed to evaluate the magnitude of the damage to renal function and to identify the risk or protective factors in renal toxicity. The retrospective study was performed using 81 consecutive patients who underwent at least three cycles of cisplatin chemotherapy. The results indicate an average decline in glomerular filtration rate (GFR) of 9 ml/min. Women appear to be less by a decline in renal function (a relative decline of GFR of -5% for women compared to -9% for men). The decline in GFR was found to be proportional to age; overweight (not obese) individuals had the best renal function behavior under cisplatin treatment, while the association of anaemia appears to be a risk factor for renal toxicity. The use of cisplatin in oncology in the last years may have decreased, either by using combination chemotherapy instead of monotherapy, or by its displacement by newly discovered treatments (e.g., immunotherapy in lung cancer). Therefore, it is possible that the profile of patients who are exposed to this drug and the duration of exposure have been modified compared to previous studies. The objectives of the present study were to assess the magnitude of the renal function damage during cisplatin treatment and to identify the risk and the protective factors in term of renal toxicity.

Toric intraocular lens implantation - atypical cases.

Objective: To describe the results of toric intraocular lens (IOL) implantation in three atypical cases (four eyes) with cataract and corneal astigmatism: one with bilateral keratoconus, one with pellucid marginal degeneration and one with buphthalmos due to congenital glaucoma. Methods: Three patients (four eyes) with corneal astigmatism (one with bilateral keratoconus, one with pellucid marginal degeneration and one with buphthalmos due to congenital glaucoma) underwent cataract surgery by standard phacoemulsification and the implantation of toric IOLs in the capsular bag. The presence of corneal astigmatism was identified by automated keratometry and confirmed by Scheimpflug-based corneal tomography. The toric IOL implanted in all cases was a single-piece AcrySof Toric IOL (Alcon Laboratories, Inc.). Postoperative visual acuity, the reduction in the refractive astigmatism, the spherical equivalent (SE) and the rotational stability of the toric IOL were recorded for all the patients. Results: Visual acuity increased and the refractive astigmatism decreased in all cases. In Case 1, the right eye achieved a postoperative uncorrected visual acuity (UCVA) of 20/ 20, a decrease in the refractive astigmatism from -3 DCyl to -0.75 DCyl and a spherical equivalent (SE) of -0.25. The left eye presented with a best-corrected visual acuity (BCVA) of 20/ 20, a decrease in the refractive astigmatism from -1.50 DCyl to -1.25 DCyl and a SE of -0.25. In Case 2, the postoperative UCVA was 20/ 20, with a decrease in the refractive astigmatism from -5.5 DCyl to -1 DCyl and a SE for the right eye of 0.00 D. In Case 3, the postoperative BCVA was 20/ 20, with a decrease in the refractive astigmatism from -4.75 DCyl to -1.50 DCyl and a SE of +1.25. No misalignment of the axis of the toric IOL was observed in any patient at subsequent follow-ups. The postoperative visual acuity was satisfactory for all the patients. Conclusions: Toric intraocular lenses can be an effective option for implantation in patients with cataract and corneal astigmatism in atypical situations such as mild to moderate keratoconus, pellucid marginal degeneration and buphthalmos due to congenital glaucoma. Predicting the refractive outcome is difficult in atypical cases and the surgeon should have accuracy and consistency in the preoperative measurements, for achieving satisfactory postoperative results.

Cumulative visual impact of two coagulability disorders: A case report.

Cumulative visual impact of two coagulability disorders were reviewed by presenting a case of a young female patient with a spontaneous abortion and two thromboembolic events in 8 years, whose visual function was severely affected. The particularities of her genetic constellation regarding the retinal circulation are also discussed. The patient developed a central retinal artery occlusion in the right eye during pregnancy in 2010, which led to an extended hematological workup that revealed presence of MTHFR C677T and MTHFR A1298C heterozygote mutations. The screening for myeloproliferative disorders showed JAK2 V617F gene mutation. Test results confirmed the diagnosis of thrombophilia and essential thrombocythemia and she was recommended permanent treatment with low molecular weight heparin, platelet antiaggregant, peripheral vasodilator and neuroprotectors. Despite the treatment, the patient developed central retinal vein occlusion in the fellow eye 8 years after the first thromboembolic event. The visual acuity for the right eye (0.9 logMAR) remained poor and the visual acuity for the left eye recovered completely (from 0.3 logMAR to 0 logMAR). However, new retinal artery or vein occlusions could occur in the future and there is also a risk of thrombosis in other areas, such as cerebral, pulmonary or renal, due to the general coagulability imbalance.

Triamcinolone acetonide induces sterile endophthalmitis in patients with intermediate uveitis: A case report series.

Due to their anti-inflammatory, antiangiogenic and antiedematous properties, corticosteroids have been commonly used in the treatment of retinal diseases. Intravitreal administration of steroids offers the maximal drug efficacy and the lowest risk of systemic side effects. The authors report three cases of presumed sterile endophthalmitis induced by triamcinolone acetonide (TA) in three eyes with intermediate non-infectious uveitis. Each patient received a single intravitreal injection of TA of 4 mg. Because of the intense vitreous inflammatory reaction, retina examination and the optical coherence tomography could not be performed, although vitreous opacities were observed on the ocular ultrasound. The dense vitreous opacity is a defining factor, the anterior segment inflammation is mild to moderate and a hypopyon is present, which may be a sterile inflammatory reaction or the triamcinolone material itself. In cases of sterile endophthalmitis, the visual acuity increases progressively as the intraocular inflammation diminishes. Local treatment with topical antibiotics, prednisolone acetate and cycloplegic eyedrops is recommended to control the inflammatory reaction.

Intraoperative flap-related complications in FemtoLASIK surgeries performed with Visumax® femtosecond laser: A ten-year Romanian experience.

Incidence and clinical results of intraoperative flap and interface-related complications were investigated after Femtosecond-LASIK surgery, where flap creation was performed with VisuMax® femtosecond laser. A retrospective 10-year cohort study was conducted including all eyes treated for all refractive errors by Femtosecond-LASIK technique. All the flaps were made by the same refractive surgeon with the VisuMax® (Carl Zeiss Meditec) femtosecond laser. We report the intraoperative flap and interface-related complications in these eyes, also describing their management. The study included 4,032 eyes. Flap and interface-related complications were: opaque bubble layer (OBL) 21.18%, suction loss 1.29%, difficult docking 0.69%, difficult dissection of the flap 0.59%, bleeding from limbal blood vessels 0.35%, de-epithelialization of the flap 0.12%, and interface debris 0.025%. These situations were appropriately addressed, with favorable outcomes. Flap creation is an important step in LASIK surgery. The predictability and safety have improved since the flap incision is assisted by a femtosecond laser, but complications of the flap and interface can still occur during the flap creation. Refractive surgeons should be aware and properly manage any unusual situation.

Accuracy of five intraocular lens formulas in eyes with trifocal lens implant.

Accuracy of intraocular lens (IOL) calculation formulas SRK/T, Hoffer Q, Holladay 1, Haigis and Barrett Universal II were compared in prediction of postoperative refraction for multifocal and implants using a single optical biometry device. The authors included 88 refractive lens exchange and cataract surgeries, with AcrySof IQ PanOptix implant (Alcon Laboratories, Inc.). All eyes were divided into three groups based on axial length (AL), group 1: <22 mm (14 eyes), group 2: 22-24.5 mm (68 eyes) and group 3: >24.5 mm (6 eyes). The refractive prediction error (RPE) and mean absolute error (MAE) were calculated for 5 different formulas: SRK/T, Hoffer Q, Holladay 1, Haigis and Barrett Universal II. For eyes with the AL between 22 mm and 24.5 mm the greatest percentage of eyes with RPEs within ±0.25 D was 32.4% for Haigis formula, followed by Barrett Universal II, Hoffer Q and Holladay 1 with 29.4%. The percentage of eyes with RPEs within ±0.50 D was 100% only for Barrett Universal II and Holladay 1, 94.1% for SRK/T and 91.2% for Haigis and Hoffer Q. The first and third group with AL <22 and >24.5 mm were too small to have statistical significance due to the reluctancy to use multifocal IOLs on extreme ALs. ANOVA test showed no statistical difference (P=0.166) between the RPEs measured for each formula in this cohort. This study showed no statistical difference between formulas for this trifocal lens implant. There was a tendency for the RPE to be within ±0.25 D for most of the eyes with the Haigis formula, and within ±0.50 D for all the eyes with the Barrett Universal II formula in the group with the AL between 22 and 24.5 mm.

Giant and multiple cardiac papillary fibroelastomas masquerading as acute cerebrovascular events.

Cardiac papillary fibroelastomas are rare benign cardiac tumors. Their clinical significance results from their very high propensity for embolization. We present two such cases, which are rare regarding the size and multiplicity of these tumors.

Bevacizumab in Wet AMD treatment: A tribute to the thirteen years of experience from the beginning of the anti-VEGF era in Romania.

This study aimed to identify and describe anatomical and functional changes on short (1-3 months) and medium (6-12 months) term after intravitreal injections of bevacizumab (Avastin, Genentech) in patients with choroidal neovascularization (CNV) in the context of exudative form of age-related macular degeneration (AMD). We performed a retrospective, analytical, interventional study, based on a series of cases with exudative form of AMD, which also comprised a prospective component related to the inclusion and treatment of the patients with a very new interventional method for that time (2006) and the follow-up of the effects of intravitreal injection of bevacizumab (1.25 mg) therapy in three monthly doses for short (1-3 months) and medium (6-18 months) periods of time. The follow-up of these patients was made by determining visual acuity (VA) as best corrected visual acuity (BCVA) at baseline and at every visit, slit lamp examination with contact or noncontact lenses each time, and optical coherence tomography and/or angiofluorography, applied only for certain patients, at various times of the study. In total, 376 intravitreal injections were administered to 117 eyes of 96 patients. The VA improved in the assessment of 3 months in 77 eyes (66%), either subjective (by the patient) or objectively quantified (by the physician). In 40 eyes (34%), there was no change in VA. In patients for whom optical coherence tomography could be performed, a significant reduction of the macula's thickness was found. The use of bevacizumab in subretinal neovascular membrane treatment is effective and safe on short and medium term, with the improvement of BCVA and reduction of macular edema in a significant number of cases.

Clinical features in toxic coma in children.

The purpose was to identify rapidly the etiology of toxic coma in children, to appreciate the severity of the coma, to detect elements of gravity based on associated clinical signs and symptoms and to evaluate the initial treatment. Toxic coma is a medical emergency, especially in a Pediatric Emergency Department, requiring rapid and precise evaluation. The key objectives in the evaluation and management of coma in children are: detecting severity characteristics, depth of coma, specific clinical signs and symptoms, etiological and differential diagnostic and also initializing supportive therapy and specific treatment. This is a retrospective study, where we analyzed all patients diagnosed with coma admitted to the 'Grigore Alexandrescu' Clinical Emergency Hospital for Children over a nine-year period from 2003 to 2011. We focused on toxic coma. A prospective component related to tracking certain signs and symptoms associated with toxic coma to diagnose and initiate appropriate therapy as early as possible was also included. In this nine-year study, 750 comatose patients were included. We found that toxicants represent the main cause of coma in children. There were 445 patients diagnosed with toxic coma, representing 59.3% and 305 cases of non-toxic coma, 40.7% of all coma cases presented in ER. The etiology of toxic coma in children is dominated by alcohol and abuse substances, followed by neurologic medication. Clinical manifestations were more frequent and more severe as the coma degree increases. Associating clinical manifestations in patients with altered neurologic status of toxic cause and toxicants has an important role in practice, because it helps us recognize the frequency of association of coma complications such as: aspiration syndrome, arrhythmias and seizures.