Post-Keratoplasty Microbial Keratitis in the Era of Lamellar Transplants-A Comprehensive Review.

Microbial keratitis in a post-transplant cornea should be considered a distinct entity from microbial keratitis in a non-transplant cornea. Firstly, the use of immunosuppressive treatments and sutures in corneal transplants changes the etiology of keratitis. Secondly, corneal transplant has an impact on corneal biomechanics and structure, which facilitates the spread of infection. Finally, the emergence of lamellar transplants has introduced a new form of keratitis known as interface keratitis. Given these factors, there is a clear need to update our understanding of and management strategies for microbial keratitis following corneal transplantation, especially in the era of lamellar transplants. To address this, a comprehensive review is provided, covering the incidence, risk factors, causes, and timing of microbial keratitis, as well as both clinical and surgical management approaches for its treatment in cases of penetrating and lamellar corneal transplants.

The immunology of corneal limbal stem cells: the up-to-date approach to stem cell transplantation.

Limbal epithelial stem cells (LSC, LESC) are multipotent cells used as regenerative treatment of the cornea in patients with limbal epithelial stem cell deficiency (LSCD, LESCD). There are different types of stem cell grafting including cultivated limbal epithelial transplantation (CET) and simple limbal epithelial transplantation (SLET). The outcomes of the techniques have been assessed as similar, with differences in the sample size required during the procedures. The most important culture components for stem cell cultivation include 3T3 murine fibroblasts, human amniotic membrane (HAM), fibrin gel, and culture medium. The culture medium may be enriched with serum or not; however, xenobiotic-free materials are preferred because of the low risk of pathogen transmission. Multiple studies have defined molecules important for maintaining the function of LSC including C/EBP δ, Bmi-1, p63 α, interleukins (IL-6), epithelial structural proteins - keratins, and antibodies against epidermal growth factor receptor (EGFR). The cell phenotype of LSC has been described with factors of transplantation success rate such as a high percentage of p63 positive cells. The article emphasizes the role of recipient tissue preparation, modern cultivation techniques and pathophysiological processes in LSC transplantation effectiveness.

Progression of Rare Inherited Retinal Dystrophies May Be Monitored by Adaptive Optics Imaging.

Inherited retinal dystrophies (IRDs) are bilateral genetic conditions of the retina, leading to irreversible vision loss. This study included 55 eyes afflicted with IRDs affecting the macula. The diseases examined encompassed Stargardt disease (STGD), cone dystrophy (CD), and cone-rod dystrophy (CRD) using adaptive optics (Rtx1™; Imagine Eyes, Orsay, France). Adaptive optics facilitate high-quality visualisation of retinal microstructures, including cones. Cone parameters, such as cone density (DM), cone spacing (SM), and regularity (REG), were analysed. The best corrected visual acuity (BCVA) was assessed as well. Examinations were performed twice over a 6-year observation period. A significant change was observed in DM (1282.73/mm2 vs. 10,073.42/mm2, p< 0.001) and SM (9.83 µm vs. 12.16 µm, p< 0.001) during the follow-up. BCVA deterioration was also significant (0.16 vs. 0.12, p = 0.001), albeit uncorrelated with the change in cone parameters. No significant difference in REG was detected between the initial examination and the follow-up (p = 0.089).

Characteristics of Rare Inherited Retinal Dystrophies in Adaptive Optics-A Study on 53 Eyes.

Inherited retinal dystrophies (IRDs) are genetic disorders that lead to the bilateral degeneration of the retina, causing irreversible vision loss. These conditions often manifest during the first and second decades of life, and their primary symptoms can be non-specific. Diagnostic processes encompass assessments of best-corrected visual acuity, fundoscopy, optical coherence tomography, fundus autofluorescence, fluorescein angiography, electrophysiological tests, and genetic testing. This study focuses on the application of adaptive optics (AO), a non-invasive retinal examination, for the assessment of patients with IRDs. AO facilitates the high-quality, detailed observation of retinal photoreceptor structures (cones and rods) and enables the quantitative analysis of parameters such as cone density (DM), cone spacing (SM), cone regularity (REG), and Voronoi analysis (N%6). AO examinations were conducted on eyes diagnosed with Stargardt disease (STGD, N=36), cone dystrophy (CD, N=9), and cone-rod dystrophy (CRD, N=8), and on healthy eyes (N=14). There were significant differences in the DM, SM, REG, and N%6 parameters between the healthy and IRD-affected eyes (p<0.001 for DM, SM, and REG; p=0.008 for N%6). The mean DM in the CD, CRD, and STGD groups was 8900.39/mm2, 9296.32/mm2, and 16,209.66/mm2, respectively, with a significant inter-group difference (p=0.006). The mean SM in the CD, CRD, and STGD groups was 12.37 µm, 14.82 µm, and 9.65 µm, respectively, with a significant difference observed between groups (p=0.002). However, no significant difference was found in REG and N%6 among the CD, CRD, and STGD groups. Significant differences were found in SM and DM between CD and STGD (p=0.014 for SM; p=0.003 for DM) and between CRD and STGD (p=0.027 for SM; p=0.003 for DM). Our findings suggest that AO holds significant potential as an impactful diagnostic tool for IRDs.

Novel therapies for diabetic retinopathy.

Diabetes mellitus (DM) is a metabolic disease characterized by high blood glucose levels as well as microvascular and macrovascular changes. According to the latest statistics the growth of DM incidence is very fast. Diabetic retinopathy (DR) - one of the common DM complications - is the leading cause of blindness among professionally active people. Traditional treatment of DR including drugs controlling hyperglycemia, laser therapy, vitrectomy, and intravitreal injections of anti-VEGF is effectively administered with the effect of neovascularization and macular edema prevention. However, new potential DR therapies - focusing on a longer therapeutic effect and potentially fewer side effects - are being widely investigated. Gene therapy - targeting retinal vasculopathy or targeting retinal protection, mesenchymal stem cell injections, SGLT2 inhibitors, and islet cell transplantation have been proved to stop DR progression. The majority of the new treatment research was performed on an animal model and did not reach the final study stage. A further future human model and randomized studies with optimized delivery vectors will hopefully confirm positive outcomes of the new DR therapies.

Novel approach to antiangiogenic factors in age-related macular degeneration therapy.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss among the population above 85 worldwide. There are two main types of AMD: neovascular and dry AMD. Neovascular AMD leads to macular changes resulting from abnormal choroidal neovascularization. Untreated neovascular AMD leads to scar formation and irreversible sight deterioration. Dry AMD in consequence leads to atrophic changes of the macula. The last decades brought a breakthrough in the therapy of neovascular age-related macular degeneration by introduction of, firstly, photodynamic therapy and, later, anti-VEGF agents administered intravitreally in order to stop neoangiogenesis. However, the treatment of dry AMD is still challenging. Among the directions in dry AMD treatment, the most promising are complement cascade inhibitors and complement cascade targeted gene therapy. In the article we outline the main directions in up-to-date experimental and practical approaches to wet and dry AMD therapy with the emphasis on antiangiogenic factors and gene therapy focused on the inhibition of pathological angiogenesis.

New perspectives of immunomodulation and neuroprotection in glaucoma.

Glaucoma is the neurodegenerative disease of retinal ganglion cells. The main risk factor for glaucoma is increased intraocular pressure. The processes leading to cell death due to presence of the injury factor comprise multiple molecular mechanisms, as well as the immunological response. The knowledge of immunological mechanisms occurring in glaucomatous degeneration makes it possible to introduce glaucoma treatment modulating the cellular degradation. The glaucoma treatment of the future will make it possible not only to lower the intraocular pressure, but also to moderate the intracellular mechanisms in order to prevent retinal cell degeneration. Citicoline is a drug modulating glutamate excitotoxicity that is already in use. Rho kinase inhibitors were found to stimulate neurite growth and axon regeneration apart from lowering intraocular pressure. The complementary action of brimonidine is to increase neurotrophic factor (NTF) concentrations and inhibit glutamate toxicity. Immunomodulatory therapies with antibodies and gene therapies show promising effects in the current studies. The supplementation of NTFs prevents glaucomatous damage. Resveratrol and other antioxidants inhibit reactive oxygen species formation. Cell transplantation of stem cells, Schwann cells and nerve extracts was reported to be successful so far. Our review presents the most promising new strategies of neuroprotection and immunomodulation in glaucoma.

Immunological and molecular basics of the primary open angle glaucoma pathomechanism.

Glaucoma is a degenerative process of the optic nerve. Increased intraocular pressure is believed to be the main factor leading to the glaucomatous damage. The in vitro and in vivo animal glaucoma research models provide insight into the molecular changes in the retina in response to the injury factor. The damage is a complex process incorporating molecular and immunological changes. Such changes involve NF kB activity and complement activation. The processes affect the human antigen, JNK, MAPK, p53, MT2 and DBA/2J molecular pathways, activate the autophagy processes and compromise neuroprotective mechanisms. Activation and inhibition of immunological responses contribute to cell injury. The immunological mechanisms of glaucomatous degeneration include glial response, the complement, tumor necrosis factor α (TNF-α) pathways and toll-like receptors athways. Oxidative stress and excitotoxicity are factors contributing to cell death in glaucoma. The authors present an up-to-date review of the mechanisms involved and update on research focusing on a possible innovative glaucoma treatment.

Cowpox: How dangerous could it be for humans? Case report.

Cowpox is a rare zoonosis transmitted to humans mainly from cats. The disease usually causes skin lesions; however, the ocular form may lead to other serious complications. We describe a case of cowpox in a rare location of the upper eyelid of an immunocompetent male, which lead to necrosis of the upper eyelid, keratitis and leucomatous opacity, and the neovascularization of the cornea. The patient underwent several surgeries, including reconstruction surgery of the eyelids, correction of the medial canthus, and corneal neurotization with supraorbicular nerve transplantation. Suspicion of cowpox should be made in patients where there are poorly healing skin lesions accompanied by a painful black eschar with erythema and local lymphadenopathy. Ocular cowpox may lead to serious complications and possibly mimic anthrax. Diagnosis of cowpox can be confirmed by detection of cowpox virus DNA by polymerase chain reaction. Patients should be advised to protect themselves while handling sick animals.

Infectious mononucleosis-like syndrome with high lymphocytosis and positive IgM EBV and CMV antibodies in a three-year-old girl.

Primary Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection usually affects preadolescent children or young adults, causing similar clinical presentation. Signs and symptoms are typically mild, and the majority of clinical and laboratory findings resolve spontaneously within one month after onset. In adulthood, the risk of fulminant EBV infection and severe complications is much higher, which may be related to increasing memory CD8+ T-cell population with age. It is still not clear what exactly triggers T-cell clonal proliferation. Animals model studies on heterologous immunity between viruses revealed that pre-existing memory T-cells may contribute to excessive immune response during subsequent infection with a new, unrelated pathogen. A 3.5-year-old girl was admitted to hospital with a suspicion of lymphoproliferative disorder. Peripheral blood smear revealed a massive lymphocytosis (61,600 cells/µl) with 62% share of atypical lymphocytes. The clinical presentation and positive EBV and CMV IgM test strongly suggested infectious mononucleosis syndrome as a result of EBV and CMV coinfection.