Visual Function Improvement after Plasma Exchange Therapy for Acute Optic Neuritis in Neuromyelitis Optica Spectrum Disorders: Case Series and Review.

OBJECTIVE: Neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) are autoimmune-mediated central nervous system disorders distinguished by the presence of serum aquaporine-4 IgG antibody (AQP4-Ab). The clinical panel comprises severe optic neuritis (ON) and transverse myelitis, which can result in incomplete recovery and a high risk of recurrence. METHODS: This study aimed to evaluate the visual outcomes of three patients with severe acute ON in NMOSD that was non-responsive to intravenous methylprednisolone (IVMP), who received plasma exchange therapy (PLEX). We included three patients (P1, P2 and P3) with severe acute ON who had no improvement after IVMP treatment and were admitted to the ophthalmology department at the Emergency University Hospital Bucharest from January 2022 to September 2023. All three patients with ON were diagnosed in accordance with the criteria described by the Optic Neuritis Treatment Trial. All the subjects were experiencing their first attack. RESULTS: The mean recruitment age was 35.3 ± 7.71. All patients were seropositive for the AQP4 antibody. All patients were tested for serum myelin oligodendrocyte glycoprotein (MOG) antibody but only one showed a positive test (P3). Lesions visible in orbital MRI indicated the involvement of retrobulbar, canalicular and/or intracranial segments. All three subjects had no response or incomplete remission after an IVMP protocol (5 days of 1000 mg intravenous methylprednisolone in sodium chloride 0.9%). The mean time from onset of optic neuritis to PLEX was 37.6 days. The PLEX treatment protocol comprised five cycles of plasma exchange treatment over 10 days, with a plasma exchange session every other day. An amount of 1 to 1.5 volumes of circulating plasma were dialyzed for 2-4 h. At 1 month after the completion of PLEX therapy, BCVA and VF parameters were improved in all three patients. CONCLUSION: The treatment of ON remains subject to debate and is somewhat controversial. Plasma exchange must be considered as a rescue therapy when IVMP is insufficient for AQP4-ON patients. This study revealed that PLEX treatment effectively improves the visual outcomes of patients experiencing their first attack of severe acute isolated ON after high-dose IVMP treatment. This study suggests that PLEX may be associated with improved visual outcomes in NMOSD acute optic neuritis.

Titanium Implants Coated with Hydroxyapatite Used in Orbital Wall Reconstruction-A Literature Review.

With the increasing incidences of orbital wall injuries, effective reconstruction materials and techniques are imperative for optimal clinical outcomes. In this literature review, we delve into the efficacy and potential advantages of using titanium implants coated with nanostructured hydroxyapatite for the reconstruction of the orbital wall. Titanium implants, recognized for their durability and mechanical strength, when combined with the osteoconductive properties of hydroxyapatite, present a potentially synergistic solution. The purpose of this review was to critically analyze the recent literature and present the state of the art in orbital wall reconstruction using titanium implants coated with nanostructured hydroxyapatite. This review offers clinicians detailed insight into the benefits and potential drawbacks of using titanium implants coated with nanostructured hydroxyapatite for orbital wall reconstruction. The highlighted results advocate for its benefits in terms of osseointegration and provide a novel strategy for orbital reconstruction, though further studies are essential to establish long-term efficacy and address concerns.

Ocular adverse effects of anti-cancer chemotherapy.

Cancer ranks as the second leading cause of mortality in Europe, following cardiovascular diseases. Every year, 2.6 million people are diagnosed with this disease, and 1.2 million die. It has an impact not only on individual health but also on society and the economy. The survival rate has improved with the introduction of new diagnostic methods and anti-cancer chemotherapy. While more aggressive chemotherapeutic regimens and combination therapies have demonstrated efficacy against cancer cells, they also have detrimental effects on normal cells, leading to systemic and ocular adverse reactions associated with cytotoxicity, inflammation, and neurotoxicity. Consequently, we have an increased survival rate, but the appearance of these ocular adverse effects decreases the quality of life. Ocular toxicity induced by chemotherapeutic agents is often underestimated. While prevention may not be possible, proper management by an ophthalmologist, an integral part of the oncology patient's medical team, is crucial. The ophthalmologist should assess the patient before initiating chemotherapeutic treatment and continue monitoring throughout to identify any adverse ocular reactions resulting from the systemic chemotherapy. This article aimed to briefly highlight the adverse reactions occurring at the ocular surface in patients undergoing chemotherapeutic treatment. Fortunately, these ocular side effects are limited only to the period in which the chemotherapeutic treatment is done, with most of them disappearing a few weeks after stopping the treatment.

Uncommon association between vascular Ehlers-Danlos syndrome and ocular complications.

Ehlers-Danlos syndromes (EDS) represent a group of rare inherited disorders that affect connective tissues. There are 13 types of disease, most of them affecting joints or skin; symptoms usually include loose joints, joint pain, stretchy velvety skin, abnormal scar formation. However, the most serious type of disease is vascular EDS (vEDS), or EDS type 4 because patients may suffer vessels dissections or internal organs lesions, followed by bleeding, which endangers patient's life, but also thromboembolic events. We present two clinical cases of vEDS managed in our clinic in 1 year distance. In both cases, patients were active young persons (in their thirties, and respectively, twenties), both with multiple non-traumatic vascular dissections, and severe ocular complications: arterio-venous fistula with massive exophthalmia, and central retinal artery occlusion, respectively. Both cases were challenging since the life of the patients were threatened by their condition. However, in both cases, prompt treatment and finding the right trigger of the ocular pathology and vascular injuries helped doctors to provide proper and prompt medical care, in order to prevent future similar events to happen and to preserve a good quality of life for these patients.

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.

Safety and Outcomes of Intravitreal Aflibercept in Diabetic Macular Edema - A Systematic Review.

BACKGROUND: Recent evidence on the role of vascular endothelial growth factor (VEGF) in the pathogenesis of ischemia and microvascular hyperpermeability leading to macular edema has brought anti-VEGF intravitreal therapy into the limelight. OBJECTIVE: We performed a systematic literature review focusing on the outcomes and safety of the intravitreal use of aflibercept in diabetic macular edema. METHODS: The studies documented cases with at least three consecutive intravitreal injections of aflibercept (IVA) repeated monthly with a follow-up period of at least one year. The outcomes were evaluated in terms of reported functional and anatomical improvement of the macula, as reflected by changes in visual acuity and macular thickness measured by Optical Coherence Tomography (OCT). In addition, for safety assessment, all reported local and general adverse effects were analyzed. RESULTS: All studies showed an overall significant anatomical and functional improvement. In patients with the 5 IVA monthly at the beginning of the therapy, the visual gain at 52 weeks varied widely between 5 and 18.9 EDRS letters, with a mean value of 9.48 letters. The higher gain was obtained in treatment naïve patients, with worse VA and increased CST at baseline. The lower gain was obtained in patients previously treated with anti- VEGF. Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events were not statistically different between the aflibercept group and the laser group. CONCLUSION: Intravitreal aflibercept therapy provides significant improvement in visual acuity and a good safety profile. Randomized studies are needed to document the optimal frequency of intravitreal injections for optimal treatment.

Biocompatible Materials for Orbital Wall Reconstruction-An Overview.

The reconstruction of an orbit after complex craniofacial fractures can be extremely demanding. For satisfactory functional and aesthetic results, it is necessary to restore the orbital walls and the craniofacial skeleton using various types of materials. The reconstruction materials can be divided into autografts (bone or cartilage tissue) or allografts (metals, ceramics, or plastic materials, and combinations of these materials). Over time, different types of materials have been used, considering characteristics such as their stability, biocompatibility, cost, safety, and intraoperative flexibility. Although the ideal material for orbital reconstruction could not be unanimously identified, much progress has been achieved in recent years. In this article, we summarise the advantages and disadvantages of each category of reconstruction materials. We also provide an update on improvements in material properties through various modern processing techniques. Good results in reconstructive surgery of the orbit require both material and technological innovations.

Tyrosine kinase inhibitors in breast cancer (Review).

Anti-epidermal growth factor receptor (EGFR)-targeted therapy has been intensely researched in the last years, motivated by the favorable results obtained with monoclonal antibodies in HER2-enriched breast cancer (BC) patients. Most researched alternatives of anti-EGFR agents were tyrosine kinase inhibitors (TKIs) and monoclonal antibodies. However, excluding monoclonal antibodies trastuzumab and pertuzumab, the remaining anti-EGFR molecules have exhibited disappointing results, due to the lack of specificity and frequent adverse side effects. TKIs have several advantages, including reduced cardiotoxicity, oral administration and favorable penetration of blood-brain barrier for brain metastatic BC. Lapatinib and neratinib and recently pyrotinib (approved only in China) are the only TKIs from dozens of molecules researched over the years that were approved to be used in clinical practice with limited indications, in a subset of BC patients, single or in combination with other chemotherapy or hormonal therapeutic agents. Improved identification of BC subtypes and improved characterization of aggressive forms (triple negative BC or inflammatory BC) should lead to advancements in shaping of targeted agents to improve the outcome of patients.

Corneal Biomechanical Changes in Third Trimester of Pregnancy.

Background and Objectives: There is a clear evidence that pregnancy is associated with high production of sex hormones. During the first, second and third trimester of pregnancy, blood hormones levels increase gradually. Cells with affinity for sex hormones have been identified in different ocular tissues, such as: lid, lacrimal gland, meibomian gland, bulbar and palpebral conjunctivae, cornea, iris, ciliary body, lens, retina (retinal pigment epithelium) and choroid. This is why pregnancy is associated with changes at ocular level, involving anterior and posterior segments. Several clinical trials have been made trying to highlight changes in corneal biomechanics during pregnancy. By conducting this review, we want to evaluate both the changes in parameters that define corneal biomechanics and intraocular pressure values in pregnant. Materials and Methods: Following a systematic search in the literature related mainly to changes in corneal biomechanics during pregnancy, focusing on the paper published in the last decade, we included in a meta-analysis the cumulative results of three prospective comparative studies. Results: Important changes in corneal biomechanics (corneal hysteresis and corneal resistance factor) parameters were observed in women in the third trimester of pregnancy, but these variations were not statistically significant. Also, a decrease in intraocular pressure was mentioned in these women, but only the corneal compensation intraocular pressure showed a decrease with statistical significance. Conclusions: A decrease in corneal compensatory intraocular pressure was observed in pregnant women in the third trimester of pregnancy, but without other statistically significant changes resulting from the analysis of the other three parameters (corneal hysteresis, corneal resistance factor and Goldmann-correlated intraocular pressure).

Correlations between corneal biomechanics and specular microscopy in patient with cataract.

This study aimed to analyze the connection between corneal biomechanics (corneal hysteresis, CH) and endothelial cell density of cornea (mean endothelial cell density, MCD) in patients diagnosed with cataract. This retrospective, observational study was performed in the Ophthalmology Clinic of the University Emergency Hospital in Bucharest. Of 60 patients (120 eyes) with cataract, who were included in this study, we analyzed the CH values obtained using with the Ocular Response Analyzer (ORA) and the MCD values obtained using the specular microscopy. The study groups comprised both men and women with ages ranging from 45 to 63 years. Patients were divided into three study groups according to CH values. In each batch, the CH values obtained with the Ocular Response Analyzer (ORA) were correlated with age, gender and MCD, then the subgroups were compared. All the data gathered showed no correlation to be statistically significant regarding the biomechanical properties of the cornea and the corneal endothelial cell density in patients with cataract.

The role of Visual Evoked Potential (VEP) in monitoring the progression and in guiding the treatment of glaucoma patients with poor compliance.

Objectives: The objectives of the present study were to analyze the possibility of using pattern VEPs (VEP of pattern type) in glaucoma patients and their role in the follow-up and coordination/ management of anti-glaucoma treatment. Patients and Methods: This is a prospective study on 54 eyes of 30 consecutive glaucoma patients, whose compliance capacity did not allow automatic perimetry and OCT scan to be carried out. The patients were divided into two groups: group A - the study group and group B - the control group. All patients underwent FO exam and pachymetry, plus VEP exam for group A patients. Patients were analyzed at the initial visit and at 1 month, 3, 6, 12 months. Statistical analysis was made using t-test, ANOVA, Fisher test and Pearson correlation coefficient. Results: These participants presented a positive correlation between C/ D ratio and the latency of the P100 wave at 1 degree and a negative correlation between C/ D ratio and the amplitude of the P100 wave both at 1 degree (60 arc minutes) and at 0.25 degrees (15 arc minutes). During the study, the values of the latent P100 changed statistically at 6 months and at 1 year. Using all the data, the authors of the study considered it necessary to modify the treatment for 2 patients out of 13 in group B and for 9 patients out of 16 in group A (p = 0,02892). Conclusions: VEP supplies additional/ further data that significantly help guiding the treatment and monitoring the progression, therefore, it should be part of the routine examination for these patients. Further studies are necessary to deepen our understanding of the visual evoked potentials utility.

Visual evoked potential in the early diagnosis of glaucoma. Literature review.

Visual evoked potentials (VEP) are a significant visual electrophysiological diagnostic exam, which can be used as a suitable objective measure of optic nerve function. The topic was greatly debated and many correlations between the magnitude of the VEP latency parameters and parameters of Humphrey static perimetry suggested that the abnormal cortex responses in patients with glaucomatous changes could be tested by both electrophysiological and physical methods. Moreover, the optic nerve glaucomatous damage observed by reduction in ganglion cell layer and retinal fibre layer thickness through SD-OCT tests, which are known to precede Humphrey visual field defects, correlates with VEP latency parameters, thus consolidating the position of the VEP testing in glaucoma progression.

The effects of prostaglandins and endocannabinoids on iris arterial vascularization in Wistar rats - Experimental analysis.

Introduction: The iris vascular supply originates in the anterior and long posterior ciliary arteries. The endothelium influences local blood flow by releasing endothelium relaxing and contracting substances. From a functional perspective, the ocular vascular tonus adjustment is humoral and neural dependent. Objectives: The present article aims to evaluate the possible implications of topical administration of selective COX2 and nonselective COX inhibitors generically named nonsteroidal anti-inflammatory drugs (NSAIDs) and their possible interactions with the endocannabinoid system and the way they could interfere with the vascular tone at the level of ocular iris territory in Wistar rats. Materials and methods: Experimental protocol on Wistar rats was performed in accordance with present laws regarding animal welfare and ethics in animal experiments (Directive 86/ 609EEC/ 1986; Romanian Law 205/ 2004; Romanian Laws 206/ 2004, 471/ 2002 and 9/ 2008; Romanian Order 143/ 400). The studied substances were instilled topically under general anesthesia, and images of the rat iris vessels were captured over a period of 10 minutes. The obtained images were further analyzed using an appropriate hardware and software program. Results: The nonselective NSAIDs induced vascular dilation in the iris vessels, while the selective COX2 inhibitors determined a variable degree of vasoconstriction. Conclusion: In view of the results of this experiment and the added evidence found in literature, we consider that further research will show the potential benefits for the additional use of NSAIDs in ocular pathology, otherwise unaffected by this medication until the present time (for example, glaucoma treatment).

Rare ophthalmology diseases.

Rare ocular pathology has an important impact on the quality of life of patients because often the damage is bilateral and, although asymmetric, causes a significant decrease in visual acuity. Because it may be asymptomatic until a relatively late stage, diagnosis is frequently delayed. A general understanding of the disease pathophysiology, diagnosis, and treatment may assist primary care physicians in referring high-risk patients for comprehensive ophthalmological examination and for a more active involvement in their care. Moreover, a significant percentage of these orphan diseases do not have treatment approved by the FDA. The examination and monitoring of patients with rare ophthalmological disorders represents a key component of an ongoing project at the University Emergency Hospital, Bucharest, Romania - Ophthalmology Clinic. Rare disease registries are leading tools for the development of clinical research for rare diseases, improvement of patient access to new diagnostic methods, follow-up and new emerging therapies. As of this moment, the European list of rare diseases includes 53 ophthalmological diseases, which are classified as rare diseases and another 103 systemic diseases with ophthalmological involvement, out of a total of 7000 rare diseases.

Endocannabinoid System and Ocular Vascularization.

The focus of this review is the role of endocannabinoid system in ocular and systemic circulation. By critically examining preclinical and clinical research, we explore the cannabinoid receptors localization and vascular implications as well as their interaction with other anti-inflammatory drugs. The objective is to transfer knowledge on the use of cannabinoids, specifically their effect on ocular circulation and intraocular pressure, and provide a better understanding of the endocannabinoid system complexity in modulating local and systemic circulations in order to identify potential uses and limitations of cannabinoid-based therapeutics.

Intraocular Pressure, Axial Length, and Refractive Changes after Phacoemulsification and Trabeculectomy for Open-Angle Glaucoma.

PURPOSE: To compare changes in intraocular pressure (IOP), axial eye length (AEL), and refractive outcome in primary open-angle glaucoma patients undergoing cataract surgery and trabeculectomy in dependence of the sequence of surgeries. MATERIALS AND METHODS: We retrospectively analysed 48 eyes. The changes in refraction, intraocular pressure, and axial eye length were analysed after surgery. In group A (21 subjects), phacoemulsification was performed before trabeculectomy, and in group B (27 subjects), trabeculectomy was performed before phacoemulsification with a minimum time span between interventions of 6 months. RESULTS: The reduction in IOP and the decrease in AEL after trabeculectomy were significant after 6 and 12 months postsurgery (p < 0.001 each). The decrease in AEL was 0.42 ± 0.11% at 6 months after surgery and 0.40 ± 0.13% after 12 months from surgery; this decrease in AEL was comparable between the groups. The refractive outcome was significantly different between the groups (group A: 0.35 ± 0.75 dpt, group B: -0.05 ± 0.36 dpt, p = 0.018); in group A, trabeculectomy caused a hyperopic shift of 0.34 ± 0.44 dpt (p = 0.002) at 12 months postsurgery. CONCLUSION: IOP reduction after trabeculectomy causes AEL shortening. The effect on refractive outcome depends on the sequence of surgeries. Better refractive outcome is achieved if phacoemulsification is performed after trabeculectomy.

"Triple positive" breast cancer - a novel category?

Breast cancer (BC) biology is of outmost importance for its therapeutic management and for establishing patients' outcome. Breast cancer has been divided in subtypes depending on the presence of hormone receptors (HRs) for estrogen and progesterone and human epidermal growth factor receptor 2 (HER2) gene amplification. Recently, a distinct subcategory has been analyzed from the group of HER2-enriched BC with positive HR, namely HER2 positive with high levels of hormone receptor expression, suggestively named "triple positive" breast cancer. We aim to review current evidence on this subtype of BC, from the molecular mechanisms regulating its behavior to the current standard treatment outcome in order to establish whether it qualifies as a new distinct subtype of BC. Its biology is dominated by the crosstalks between HR pathway and HER2 pathway, which might be responsible for the development of rapid resistance to treatment, because of estrogen receptor up-regulation and alternate regulatory pathways activation when anti-HER2 agents are used. "Triple positive" subtype has apparently similar outcome when treated with chemotherapy alone, compared to chemotherapy and anti-HER2 agents treatment. It resembles more to luminal A breast cancer, with positive HR and HER2 negative. However, most of the clinical evidence is provided by retrospective trials with multiple potential biases. Treatment of "triple positive" subtype of BC with anti-HER2 agents and chemotherapy remain standard until stronger evidence will be available. Whether "triple positive" category should be regarded as a separate entity with distinct characteristics and management has to be demonstrated in future better designed trials.

Duodenal gastrointestinal stromal tumor presenting as pancreatic head mass - a case report.

Duodenal gastrointestinal stromal tumors (GISTs) are uncommon. Tumors arising from the first and the second part of the duodenum (DI and DII, respectively) can be wrongly diagnosed as pancreatic mass. We present a case of a 59-year-old woman who came with abdominal pain and severe upper gastrointestinal bleeding (hemoglobin 3.5 g÷dL). A solid, heterogeneously enhancing neoplasm in the head of the pancreas was revealed preoperatively by an abdominal computed tomography scan. A diagnosis of GIST was suggested. On exploratory laparotomy, there was a large mass which appeared to be originating from duodenum or from head of pancreas. Intraoperative histopathological diagnosis was GIST. Histopathology showed spindle cell tumor with cytoplasmic eosinophilia and foci of necrosis. The mitotic count was less than 5÷50 high power fields (HPFs). Tumor was involving duodenal muscularis propria, with no infiltration in the duodenal epithelial layer and the pancreas. Immunohistochemical study revealed positive staining for CD117. The tumor was finally diagnosed as GIST arising from the duodenal wall, growing exophytically and attached to the common bile duct and pancreas, without infiltrating the pancreas. Duodenal gastrointestinal stromal tumors can grow exophytically into a large mass and involve the pancreas without infiltrating microscopically and present as pancreatic head mass.

Retinal changes in diabetic patients without diabetic retinopathy.

PURPOSE: The purpose of this study was to measure retinal vessel caliber and to examine early changes in macular thickness using optical coherence tomography (OCT). We evaluated to what extend vascular caliber and macular thickness differed between patients with type 2 diabetes mellitus without diabetic retinopathy compared with healthy individuals. METHODS: 26 diabetic patients without diabetic retinopathy and 26 normal participants without any retinal and optic nerve diseases underwent ophthalmic examination, fundus photography, and OCT imaging. Temporal inferior retinal vessel diameters were measured using OCT. Also, we measured macular thickness in nine ETDRS subfields using Cirrus OCT. RESULTS: The mean age in the diabetic group was 61.5 years and in the control group, 55.5 years. Wider retinal arterioles and venules were found in patients with diabetes compared with healthy subjects (120 µm versus 96 µm, p<0.005 and 137 µm versus 120.5 µm, p value <0.001, respectively). In patients with type 2 diabetes mellitus, central macular thickness was significantly thinner than that of control eyes (243.5 µm versus 269.9 µm, p value <0.001). CONCLUSIONS: Our results support the hypothesis that the association between vascular damage and structural changes of the neuroretina is an early indicator of retinal impairment in patients with diabetes without diabetic retinopathy.

Necrotizing retinitis of multifactorial etiology.

Introduction. We present the case of a 73-year-old woman with osteoporosis, who presented to the emergency room with a sudden vision loss and ocular pain in the right eye, which appeared two days before. The patient mentioned loss of appetite, weight loss for three months and low fever for two weeks. Materials and methods. Among the ophthalmological findings, the most important were panuveitis, and large confluent necrotic areas in the peripheral retina. The patient was diagnosed with RE Panuveitis and acute necrotizing retinitis. Results. Blood exams showed leukocytosis and monocytosis, thrombocytosis and anemia. Further investigations showed high levels of Cytomegalovirus (CMV) anti IgG and Herpes Simplex (HS) type 1 virus anti IgM, urinary infection, and secondary hepatic cytolysis. The CT and MRI of the thorax and abdomen showed no sign of neoplastic disease, and no explanation for the CMV infection was found. The patient received general corticotherapy and antiviral therapy, and, after one month, RE BCVA was 20/ 30. Particularity of the case. Acute necrotizing retinitis in an old patient with CMV and HSV type 1, associated with secondary hepatic cytolysis, without any other immunosuppressive disease and very good outcome.