Biomarkers of ocular allergy and dry eye disease.

The most common disorders of the ocular surface are dry eye disease (DED) and ocular allergy (OA). These conditions are frequently coexisting with or without a clinical overlap and can cause a severe impact on the patient's quality of life. Therefore, it can sometimes be hard to distinguish between DED and OA because similar changes and manifestations may be present. Atopic patients can also develop DED, which can aggravate their manifestations. Moreover, patients with DED can develop ocular allergies, so these two pathological entities of the ocular surface can be considered as mutual conditions that share the same background. Nowadays, by using different techniques to collect tissue from ocular surfaces, the changes in molecular homeostasis can be detected and this can lead to a precise diagnosis. The article provides an up-to-date review of the various ocular surface biomarkers that have been identified in DED, OA, or both conditions. Abbreviations: DED = dry eye disease, OA = ocular allergy, SS = Sjogren syndrome, TBUT = tear break up time, TFO = tear film osmolarity, AKC = Atopic keratoconjunctivitis, ANXA1 = Annexin 1, ANXA11 = Annexin 11, CALT = Conjunctival associated lymphoid tissue, CCL2/MIP-1 = Chemokine (C-C motif) ligand2/Monocyte chemoattractant protein 1, CCL3/MIP-1α = Chemokine (C-C motif) ligand 3/Macrophage inflammatory protein 1 alpha, CCL4/MIP-1ß = Chemokine (C-C motif) ligand 4/Macrophage inflammatory protein 1 beta, CCL5/RANTES = Chemokine (C-C motif) ligand 5 /Regulated on Activation, Normal T cell Expressed and Secreted, CCR2 = Chemokine (C-C motif) receptor 2, CCR5 = Chemokine (C-C motif) receptor 5, CD3+ = Cluster of differentiation 3 positive, CD4+ = Cluster of differentiation 4 positive, CD8+ = Cluster of differentiation 8 positive, CGRP = Calcitonin-gene-related peptide, CX3CL1 C-X3 = C motif -chemokine ligand 1 /Fractalkine, CXCL8 = Chemokine (C-X-C motif) ligand 8, CXCL9 = Chemokine (C-X-C motif) ligand 9, CXCL10 = Chemokine (C-X-C motif) ligand 10, CXCL11 = Chemokine (C-X-C motif) ligand 11, CXCL12 = Chemokine (C-X-C motif) ligand 12, CXCR4 = Chemokine (C-X-C motif) receptor 4, EGF = Epidermal growth factor, HLA-DR = Human leukocyte antigen-D-related, ICAM-1 = Intercellular adhesion molecule 1, IFN-γ = Interferon-gamma, IgG = Immunoglobulin G, IgE = Immunoglobulin E, IL-1 = Interleukin-1, IL-1α = Interleukin-1 alpha, IL-1ß = Interleukin-1 beta, CGRP = Calcitonin-Gene-Related Peptide, IL-3 = Interleukin-3, IL-4 = Interleukin-4, IL-6 = Interleukin-6, IL-8 = Interleukin-8, IL-10 = Interleukin-10, IL-17 = Interleukin-17, IL-17A = Interleukin-17A, LPRR3 = Lacrimal proline-rich protein 3, LPRR4 = Lacrimal proline-rich protein 4, MUC5AC = Mucin 5 subtype AC, oligomeric mucus/gel-forming, MUC16 = Mucin 16, OCT = Optical coherence tomography, OGVHD = Ocular graft versus host disease, PAX6 = Paired-box protein 6, VKC = Vernal keratoconjunctivitis, TGF-ß = Transforming growth factor ß, S100 = proteins Calcium activated signaling proteins, Th1 = T helper 1 cell, Th17 = T helper 17 cell, MGD = Meibomian gland dysfunction, TFOS = Tear film and ocular surface society, SS-KCS = Keratoconjunctivitis Sicca, MMP-9 = Matrix metalloproteinase 9, MMP-1 = Matrix metalloproteinase 1, ZAG = Zinc alpha glycoprotein, CBA = Cytometric bead array, MALDI TOF-MS = matrix assisted laser desorption ionization-time of flight, SELDI TOF-MS = surface-enhanced laser desorption ionization-time of flight, IVCM = in vivo confocal microscopy, AS-OCT = anterior segment optical coherence tomography, iTRAQ = Isobaric tags for relative and absolute quantitation, LC-MS = Liquid chromatography-mass spectrometry, LCN-1 = lipocalin 1, PIP = prolactin induced protein, NGF = Nerve growth factor, PRR4 = proline rich protein 4, VIP = Vasoactive intestinal peptide, ELISA = enzyme linked immunoassay, TNF-α = tumor necrosis factor alpha, PAC = perennial allergic conjunctivitis, SAC = seasonal allergic conjunctivitis, IC = impression cytology, RT-PCR = reverse transcription polymerase chain reaction, PCR = polymerase chain reaction, APCs = antigen-presenting cells, NK cells = natural killer cells, HEL = hexanoyl-lysine, 4-HNE = 4-hydroxy-2-nonenal, MDA = malondialdehyde.

Intrastromal Injections in the Management of Infectious Keratitis.

Infectious keratitis is a major global cause of vision loss and blindness. Prompt diagnosis and targeted antibiotic treatment are crucial for managing the condition. Topical antimicrobials are the most effective therapy for bacterial keratitis, but they can lead to unsatisfactory results due to ocular perforation, scarring, and melting. Intrastromal injection is a newer technique for delivering antimicrobials directly to the site of infection and has been successful in treating severe, treatment-resistant infectious keratitis, especially when surgery is not recommended. In cases where deep stromal disease is resistant to topical treatment, intrastromal antimicrobial injections may be necessary to achieve higher drug concentration at the infection site. However, the use of intrastromal antibiotics is limited, as topical antibacterial agents have better penetration than antifungal agents. Bacterial and fungal keratitis have been extensively researched for intrastromal medication injections, while there is limited evidence for viral keratitis. This review emphasizes the potential of intrastromal antimicrobial injections as an alternative for managing severe refractory infectious keratitis. The technique offers direct targeting of the infection site and faster resolution in some cases compared to topical therapy. However, further research is needed to determine the safest antimicrobials options, minimal effective doses, and concentrations for various pathogens. Intrastromal injections may serve as a non-surgical treatment option in high-risk cases, with benefits including direct drug delivery and reduced epithelial toxicity. Despite promising findings, more studies are required to confirm the safety and efficacy of this approach.

Ocular Complications of Radiotherapy in Uveal Melanoma.

Uveal melanoma is the most common primary malignant intraocular tumor in adults. Radiation therapy has replaced enucleation and is now the preferred treatment in most cases. Nonetheless, around 70% of patients develop radiation-related complications, some of which are vision-threatening. The objective of this review is to present the most important complications associated with radiotherapy in the treatment of uveal melanoma and their pathogenesis, incidence, risk factors, and available preventive and therapeutic measures. The most common complications are cataracts, with a reported incidence ranging from 4% to 69%, and radiation retinopathy, reported in 5-68% of cases. Radiation-related complications are responsible for approximately half of secondary enucleations, the leading cause being neovascular glaucoma. A poor visual outcome is mainly associated with the presence of radiation retinopathy and radiation optic neuropathy. Therapeutic options are available for the majority of complications with the notable exception of optic neuropathy. However, many studies report a final visual acuity of less than 20/200 in more than 60% of treated eyes. Reducing complication rates can be achieved by lowering the dose of radiation, with the use of eccentric, customized plaques and careful planning of the irradiation delivery in order to protect structures vital to vision and by associating radiation therapy with other methods with the aim of reducing tumor volume.

Micropulse Transscleral Cyclophotocoagulation for Glaucoma after Penetrating Keratoplasty.

The main objective of the article was to assess the surgical outcome of micropulse transscleral cyclophotocoagulation in patients presenting with glaucoma after penetrating keratoplasty. We conducted a retrospective study that included 26 eyes of 26 patients who presented with glaucoma after penetrating keratoplasty, and who were treated using micropulse transscleral cyclophotocoagulation between January 2017 and December 2020. The surgeries were performed using the Iridex Cyclo G6 MicroPulse P3 Probe. The intraocular pressure, mean number of antiglaucoma medications, visual acuity, corneal status, and postoperative complications were analyzed. The minimum follow-up period was 12 months. The success rate after 12 months was 76.9%. The baseline median intraocular pressure was 29 mm Hg and decreased to 18 mm Hg after 12 months. The median number of antiglaucoma medications was also reduced from three preoperatively to one after one year. In seven cases (29.92%), the visual acuity decreased and, in four cases (15.38%), the corneal graft was not transparent. We concluded that micropulse transscleral cyclophotocoagulation is an effective and safe method for the treatment of glaucoma after penetrating keratoplasty.

Surgical Treatment in Silicone Oil-Associated Glaucoma.

Glaucoma is a vision threatening, not uncommon complication of eyes that have undergone pars plana vitrectomy with silicone oil endotamponade. Although most patients respond well to medical antiglaucoma therapy, there are refractory cases where surgery is required to control the intraocular pressure. This review, following a comprehensive literature search in the Medline database, aims to present the most important surgical techniques currently in use for glaucoma associated with silicone oil endotamponade and their indication depending on the mechanism of glaucoma. In cases of pupillary block, the presence of a patent iridotomy or iridectomy must be ensured, either by laser or surgically. When silicone oil is in excess and whenever the retinal status permits it, partial or complete removal of the silicone oil should be performed. Trabeculectomy has shown higher failure rates and more complications in these cases compared to other indications, so alternate methods are warranted. For very high intraocular pressures, glaucoma drainage devices and transscleral cyclophotocoagulation are the most used options, with good efficacy and safety profiles, although rarely they may have serious complications. The Ex-PRESS mini shunt has shown excellent results and lower rates of complications. For less important IOP elevations, minimally invasive glaucoma surgery and selective laser trabeculoplasty may be used, either alone or in conjunction with other methods.

Adherence to Therapy in Glaucoma Treatment-A Review.

Glaucoma is a chronic disease and the second leading cause of irreversible vision loss worldwide, whose initial treatment consists of self-administered topical ocular hypotensive eyedrops. Adherence with glaucoma medications is a fundamental problem in the care of glaucoma patients as up to 50% of patients fail to receive the intended benefits of the treatment. The literature has identified many barriers to patients' compliance, from factors depending on the type of medication administered, communication between physician and patients, to factors dependent on patients' behaviour and lifestyle. Failure to take medication as prescribed increases the risk that patients will not receive the desired benefit, which often leads to a worsening of the disease. Our aim is to synthesize the methods used for measuring adherence of patients to glaucoma therapy and the interventions used for addressing adherence, laying emphasis on a patient-centred approach, taking time to educate patients about their chronic disease and to assess their views on treatment.

Micropulse vs. continuous wave transscleral cyclophotocoagulation in neovascular glaucoma.

Neovascular glaucoma (NVG) is a refractory form of glaucoma, associated with important morbidity, for which no consensus exists regarding the optimal choice of therapy. The primary aim of our study was to compare the performances of micropulse transscleral cyclophotocoagulation (MP-TSCPC) and continuous wave transscleral cyclophotocoagulation (CW-TSCPC) in the treatment of neovascular glaucoma (NVG). A total of 24 eyes for MP-TSCPC and 22 eyes for CW-TSCPC, all with NVG were included. The procedures were performed using either the Iridex Cyclo G6 (IRIDEX Laser System), the MP3, or the G-Probe devices. Intraocular pressure (IOP), visual acuity (VA), the mean number of antiglaucoma medications, and postoperative complications were monitored. The minimum follow-up was 12 months. The success rate at 12 months was 54.5% in the CW-TSCPC group and 33.3% in the MP-TSCPC group. The mean IOP at baseline was 35.82 mm Hg for CW-TSCPC and 34.71 mm Hg for MP-TSCPC. The change from baseline in IOP at 12 months was 11.95 mm Hg in the CW-TSCPC group and -8.04 mm Hg in the MP-TSCPC group. There was a significant difference in the occurrence of serious complications (worsening of VA, hypotony, and phthisis bulbi) between the two methods, with CW-TSCPC associated with more important adverse effects (P=0.045). There was a decrease in the number of topical antiglaucoma medications in both groups: in the MP-TSCPC group from a mean number of 2.6 at baseline, to 1.7 at 3 months, followed by a slight increase to 2.1 at 12 months and in the CW-TSCPC group from 2.8 at baseline, to 1.4 at 3 months and 1.9 at 12 months. Our study concluded that both MP-TSCPC and CW-TSCPC could manage NVG, but, while CW-TSCPC revealed higher IOP control in the long term (which did not reach statistical significance), it also had a significantly lower safety profile.

Intraocular Pressure Measurement after Penetrating Keratoplasty.

Assessing the intraocular pressure is a difficult but crucial task in the follow-up of patients that have undergone penetrating keratoplasty. Early recognition of elevated intraocular pressure and/or glaucoma and establishment of the appropriate treatment is essential to ensure the best possible visual outcome for patients dealing with this feared complication. Although Goldmann applanation tonometry is still the gold standard for measuring the intraocular pressure, its limitations in postkeratoplasty eyes, due to postoperative modified corneal morphology, have led to the search for more suitable alternatives. This review is the result of a comprehensive literature search in the MEDLINE database that aims to present glaucoma in the context of perforating keratoplasty, the corneal properties with impact on ocular pressure measurement, and the results achieved with the most important tonometers that have been studied in this pathology. Goldmann applanation tonometry remains the reference for intraocular pressure assessment even in corneas after penetrating keratoplasty. However, some promising alternatives have emerged, the most important of which are the Pascal dynamic contour tonometry, the Tono-Pen XL, the ocular response analyzer, and the iCare. All have advantages and disadvantages but have proved to be appropriate alternatives, especially in cases in which Goldmann applanation tonometry cannot be used.

Diagnostic methods for the etiological assessment of infectious corneal pathology (Review).

Infectious keratitis is a leading cause of visual morbidity, including blindness, all across the globe, especially in developing countries. Prompt and adequate treatment is mandatory to maintain corneal integrity and to recover the best possible final visual acuity. Although in most of the cases practitioners chose to employ empirical broad-spectrum antimicrobial medication that is usually effective, in some instances, they face the need to identify the causative agent to establish the appropriate therapy. An extensive search was conducted on published literature before December 2020 concerning the main laboratory investigations used to identify the microbial agents found in infectious keratitis, their indications, advantages, and disadvantages, as well as the results reported by other studies concerning different diagnostic tools. At present, the gold standard for diagnosis is still considered to be the isolation of microorganisms in cultures, along with the examination of smears, but other newer techniques, such as polymerase chain reaction (PCR), next-generation sequencing (NGS), and in vivo confocal microscopy (IVCM) have gained popularity in the last decades. Currently, these newer methods have proved to be valuable adjuvants in making the diagnosis, but technological advances hold promise that, in the future, these methods will have increased performance and availability, and may become the new gold standard, replacing the classic cultures and smears.

Preoperative antisepsis in ophthalmic surgery (a review).

Endophthalmitis remains a serious complication following intraocular procedures. Preoperative prophylactic measures for endophthalmitis decrease the morbidity associated with this disease and represent a standard of care prior to ophthalmic surgery. The literature supports as measures for ocular antisepsis: povidone-iodine solution for ocular surface preparation, chlorhexidine in patients with iodine allergy and application of topical antibiotics. Povidone-iodine is regarded as the most effective antiseptic associated with significant reduction in ocular surface bacterial counts. Currently, the recommended preoperative management is the application of 5% povidone-iodine solution in the conjunctival fornix, prior to surgery. This paper reviews the preoperative measures for ocular antisepsis, used in order to decrease the risk of culture-proven endophthalmitis.

Challenges in HIV-Negative Cytomegalovirus Retinitis - case report.

We present the case of a 20-year-old girl with severe combined seronegative immunodeficiency who developed a bilateral decrease in visual acuity due to retinal necrosis. After further investigations, increased serological viral levels of Cytomegalovirus (CMV) were detected and confirmed the diagnosis of CMV retinitis in both eyes. After three weeks of systemic therapy with oral valganciclovir, her condition improved, with the best corrected visual acuity of the most affected eye changing from finger counting at presentation to 6/ 12. Although financial matters determined her to discontinue the antiviral treatment after three months, her ophthalmological status remained stable, and she resumed therapy after four weeks of pause. At the four months follow-up, despite an unchanged visual function, her general condition deteriorated. In the absence of appropriate treatment for her immunodeficiency both the patient's ophthalmological and systemic prognosis were poor.

Association of retinitis pigmentosa and advanced keratoconus in siblings.

Objective. The aim of the article was to present the rare association of retinitis pigmentosa and bilateral keratoconus in two brothers, one of whom developed corneal hydrops bilaterally, within a short period of time. Methods. A 29-year-old man presented to our service with corneal hydrops in the right eye, complaining of ocular pain and photophobia. He had a history of retinitis pigmentosa, having been diagnosed as an infant. He also had a younger brother carrying the same diagnosis. Slit lamp examination revealed bilateral keratoconus with corneal hydrops in the right eye, posterior subcapsular cataract, macular atrophy and the characteristic retinal signs of retinitis pigmentosa. The patient's brother was also examined, with the same findings being noted, apart from the corneal hydrops. We documented the changes using a slit lamp biomicroscope, a fundus camera, a corneal topography, Anterior Segment Optical Coherence Tomography and visual field testing. Right hydrops regressed in one month after hyperosmolar 5% sodium chloride treatment. However, 4 weeks later, the patient presented with the same corneal findings in the left eye. The same treatment was prescribed for the left eye. Results. Corneal hydrops regressed in both eyes with remaining paracentral corneal scars. However, no other treatment for keratoconus was suitable in the case of this patient. Discussion: Retinitis pigmentosa is currently not amenable to any form of treatment, from vitamin supplementation, medical therapy, gene transfer-based therapy, stem cell-based therapy to retinal implantation. However, molecular genetics may someday provide new therapeutic prospects, that could modify the course of RP. Conclusions. The association of retinitis pigmentosa with keratoconus is a fairly rare finding, worth taking into consideration. Also, presentation with keratoconus in such an advanced state is uncommon and, in our case, it was presumably due to the patient's reduced visual function since childhood, secondary to retinitis pigmentosa, that has prevented him from perceiving any visual modifications caused by keratoconus.