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.

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.

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.

Efficacy of conjunctival flap surgery for deep corneal ulcers.

Aim: To evaluate the clinical efficacy of a selective, partial, pedicle conjunctival flap in the treatment of deep corneal ulcers with or without perforation, resistant to medical treatment. Method: This interventional self-controlled retrospective study included 31 eyes of 31 patients with deep corneal ulcers who underwent conjunctival flap surgery in a tertiary eye care unit between 2017 and 2019. Of these, 9 eyes exhibited corneal perforation. The follow-up period was 12 months. The primary outcome measures were restoring ocular surface integrity and secondary outcome measures were improvement in visual acuity and postoperative complications encountered. Results: Out of the total of 31 patients, 17 patients (55%) were males and 14 patients (45%) were females. The mean age was 56.03 ± 15.46 years. The mean disease duration was 64.10 ± 35.01 days, the mean diameter of the ulcer was 3.61 ± 1.02 mm and the mean depth of the ulcer was 70.65 ± 20.28% of the thickness of the cornea. The etiology was extensive and the corneal ulcers were categorized as infectious (12), noninfectious (16), and unknown (3). An anatomic cure was obtained in 29 (94%) of 31 eyes. Conjunctival flap surgery was unsuccessful in 2 eyes that required evisceration. The postoperative visual acuity (BCVA) improved in 13 (42%) of the 31 eyes, decreased in 9 eyes (29%) and remained unchanged in 9 eyes (29%). The most frequent complications after conjunctival flap surgery were pseudopterygium, cataract and corneal opacity and less frequent complications were glaucoma, astigmatism, flap retraction, corneal perforation and endophthalmitis. Conclusions: Conjunctival flap surgery can successfully treat refractory deep corneal ulcers. It can restore ocular surface integrity and provide metabolic and mechanical support for corneal healing. Also, it can avoid emergency penetrating keratoplasty or create appropriate conditions for a future optic keratoplasty.

Imagery - ultrasound biomicroscopy and anterior segment Optical Coherence Tomography - in the diagnosis of anterior segment pathology.

Purpose: The aim of this paper was to show the usefulness of imagery in better documenting the pathology of the anterior segment. Methods: The article comprises clinical cases, insisting on how imagery was essential in establishing the diagnosis or the therapeutic plan. Results: Lack of imagery would have made establishing a proper diagnosis much more difficult. Conclusions: Although clinical examination is simple and offers a fairly good amount of information, some particular cases of anterior segment pathology need additional investigations, every method having its indications and limits.

Conjunctival flap surgery in the management of ocular surface disease (Review).

Literature regarding conjunctival flap surgery was reviewed to describe and discuss the rationale for this type of procedure. The conjunctival flap is an acknowledged surgery for the treatment of various corneal diseases with a chronically compromised ocular surface, such as severe dry eye, neurotrophic or neuroparalytic disease, or bullous keratopathy. The purpose of this surgery is to restore the integrity of the corneal surface and thus to prevent gradual corneal ulceration and secondary infection, as well as to ameliorate pain, reduce the need for frequent medications, improve cosmetic appearance, and offer an alternative to invasive surgery or enucleation. Since the introduction of more effective methods of treating severe ocular surface diseases, conjunctival flap surgery has rarely been the primary modality of treatment and has usually followed a range of medical and surgical treatments. The availability of improved ocular lubricants, more effective antimicrobials, bandage contact lenses, tissue adhesives, and other corneal and conjunctival surgical interventions, has reduced the need for conjunctival flaps. However, conjunctival flaps remain extremely useful in selected cases and deserve a place in the ophthalmologist's repertoire for the management of ocular surface disease.

Update on surgical management of corneal ulceration and perforation.

Corneal ulcerations are a medical emergency, and in recalcitrant cases, leading to perforation, a surgical ophthalmological emergency. The urgency of the treatment is dictated by the necessity of preventing complications that can lead to serious ocular morbidities. Medical treatment represents the first therapeutic approach and is a defining step in the further management of a patient with corneal ulceration. Multiple surgical strategies are available, but the option depends on the etiology and parameters of the ulceration: size, depth, and location.

Emergency penetrating keratoplasty in corneal perforations.

Corneal perforations represent an ophthalmological emergency due to their devastating consequences. Emergency treatment is mandatory to try to restore the anatomical integrity of the globe, to salvage useful vision as much as possible and to reduce the possible complications to a minimum. The underlying conditions or disorders responsible for corneal ulcerations, and subsequently for corneal perforations are numerous, and can be either isolated or superimposed. Emergency penetrating keratoplasty is a difficult surgical procedure that is associated with various complications, which can jeopardize the outcome of the eye.

Uncommon form of normal-tension glaucoma.

AIM: To present diagnostic particularities, assessment of prognosis, and the need for treatment in a case of normal-tension glaucoma. METHODS: - presentation of clinical changes and investigations supporting the diagnosis; - careful anamnesis that disclosed new elements, useful for the evaluation of the case. RESULTS: after a two-year follow-up period, we can ascertain that the optic atrophy is non-progressive. CONCLUSIONS: the assessment of risk factors and a rigorous anamnesis were significant for the establishment of prognosis and need for treatment.

Topical administration of Metamizole and its implications on vascular reactivity in Wistar rats- Experimental research.

Aim: The aim of this paper was to describe the possible implications of topical (ocular) administration of Metamizole on vascular reactivity of the iris in Wistar rats. No other study regarding its topical use was found. Methods: Male adult Wistar rats were anaesthetized with Ketamine 100 mg /kg body weight - injected intraperitoneally - while maintaining spontaneous respiration and the blink reflex. After selecting the area of interest (long posterior ciliary artery - LPCA), manual adjustments of the image magnitude, clarity, and brightness were made, and the experiment began. The image recording lasted 10 minutes. Results: Metamizole induced a slight vasoconstriction that started with the initial moment for all the doses used. After the topical administration of Metamizole, we did not observe an increase of the vascular diameter of LPCA in a dose dependent manner. The saline solution used as a negative control did not modify the vessel diameter. Conclusions: Metamizole (dipyrone) is a non-opioid drug, which is commonly used in human and veterinary medicine. It is the most popular first-line analgesic in various populations. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug. The high analgesic efficacy of metamizole, as well as its spasmolytic effect, makes it a very important pharmaceutical agent that could be used in the therapy of various eye disorders in humans and in animals. Abbreviations: COX = Cyclooxygenase; LPCA = Long Posterior Ciliary Artery; PRP = panretinal photocoagulation; PDR = proliferative diabetic retinopathy; Sec = second(s); VSPR = very severe non proliferative diabetic retinopathy.

Glaucoma after penetrating keratoplasty.

Penetrating keratoplasty is a surgical intervention that despite the progress of surgical techniques and of postoperative treatment continues to have numerous complications. Many of them, such as graft rejection, significant astigmatism, cystoid macular edema, or cataract lead to important limitations of the visual function. Glaucoma is possibly the most dangerous complication following PK, leading to loss of the visual potential of the eye due to irreversible damage to the optic nerve. Identifying the risk factors permits an attentive follow-up and rapid treatment of the postoperative IOP rises. Maybe the most important is that preexisting glaucoma should be rightly diagnosed and controlled before PK, medically or, if necessary, surgically. Abbreviations: PK = penetrating keratoplasty, IOP = intraocular pressure, PAS = peripheral anterior synechiae, TM = trabecular meshwork, DM = Descemet membrane, GAT = Goldmann applanation tonometry, MMC = mitomycin C, CAI = carbonic anhydrase inhibitors, 5-FU = 5-fluorouracil.

Unilateral pigmentary retinopathy--a review of literature and case presentation.

OBJECTIVES: To report a rare case of unilateral pigmentary retinopathy and describe the clinical and visual field characteristics of this particular case. METHODS: We present the case of a 30-year-old male patient with a gradual loss of the visual field on his left eye (LE) for the past 10 years, with further gradual painless loss of his central visual field in the last year, and no similar symptoms in his right eye. His past medical and ocular history were unremarkable. No family history of acquired or inherited diseases was determined. RESULTS: Based on the history, clinical findings, and visual field examination, the diagnosis of unilateral pigmentary retinopathy was established. Visual acuity and visual field in the left eye (LE) were severely affected, while in the right eye (RE), they were completely normal. CONCLUSIONS: In this case, distinct features of pigmentary retinopathy were observed only in one eye, with the fellow eye being unaffected. The diagnosis requires a long follow-up period, visual field and electrophysiological testing to rule out a delayed onset of a bilateral form of pigmentary retinopathy.

A RARER FORM OF ANGLE-CLOSURE GLAUCOMA--DIAGNOSIS AND TREATMENT.

PURPOSE: to show how we diagnosed and treated a rarer form of angle-closure glaucoma; the pathogenic mechanism was angle crowding through thick peripheral iris roll. METHODS: we show the investigations: biomicroscopy of the fundus, tonometry, pachymetry, gonioscopy, perimetry, ultrasound biomicroscopy, optical coherence tomography of the anterior segment--that helped us to diagnose the angle-closure glaucoma and its pathogenic mechanism; we also show our choice for surgery--lens extraction--and our arguments for this choice. RESULTS: first postoperative day--intraocular pressure was 14 mmHg; a week postoperatively--intraocular pressure was 13 mmHg; three months postoperatively--intraocular pressure was 13 mmHg. CONCLUSIONS: lens extraction may be a very good choice in several forms of angle-closure glaucoma.

[The significance of imaging in a case of intraorbital cystic tumor]. / Influenta investigatiilor imagistice într-un caz de tumora chistica intraorbitara.

Conjunctival inclusion cyst represents a congenital or, in most cases, an acquired disorder. The most frequent cause of an acquired conjunctival cyst is the implantation of conjunctival epithelium after surgical interventions or ocular trauma. Usually, these cysts are located supero-medially, with a stationary evolution, without a progression in dimension, but in some cases can evolve into enormous translucent cysts. Histologically, they are lined by stratified, nonkeratinized, squamous epithelium and contain desquamated cellular debris, chronic inflammatory cells and mucus, when goblet cells are present. Most cysts can be treated adequately by complete excision with marsupialization of the entire epithelial lining to prevent fluid reaccumulation.

[Peripheral ulcerative keratitis]. / KERATITA ULCERATIVA PERIFERICA.

Ulcerative keratitis is frequently associated with collagen vascular diseases and presents a predilection for peripheral corneal localization, due to the distinct morphologic and immunologic features of the limbal conjunctiva, which provides access for the circulating immune complexes to the peripheral cornea via the capillary network. Deposition of immune complexes in the terminal ends of limbal vessels initiates an immune-mediated vasculitis process, with inflammatory cells and mediators involvement by alteration of the vascular permeability. Peripheral ulcerative keratitis generally correlates with exacerbations of the background autoimmune systemic disease. Associated sceritis, specially the necrotizing form, is usually observed in severe cases, which may evolve in corneal perforation and loss of vision. Although the first-line of treatment in acute phases is represented by systemic administration of corticosteroids, immunosuppressive and cytotoxic agents are necessary for the treatment of peripheral ulcerative keratitis associated with systemic diseases.

[Ocular hypertension in herpes simplex keratouveitis]. / Hipertensiunea intraoculara în keratouveitele date de virusul herpes simplex.

The herpes simplex virus is one of the most common pathogens in humans, who are seropositive for the virus in 90% of the cases at the adult age. It determines reccurent infections in more than a third of the population and these infections depend on the immune response of the host. Ocular infections of newborns are due to the herpes simplex virus type 2, meanwhile type 1 is found predominantly at adults; almost all ocular structures can be affected. HSV-1 in the most frequent etiologic agent in infectious anterior uveitis (with the varicelo-zosterian virus) and it is responsible for 6-10% of all cases of anterior uveitis. More than half of the keratouveitides due to HSV will develop intraocular hypertension and open-angle secondary glaucoma, during reccurences and most of them will resolve after proper control of inflammation.

[Ocular ischemic syndrome--a case report]. / Sindromul de ischemie oculara- pornind de la un caz clinic.

Ocular ischemic syndrome, also known as hypoperfusion/ hypotensive retinopathy or as ischemic oculopathy is a rare ocular disease determined by chronic arterial hypoperfusion through central retinal artery, posterior and anterior ciliary arteries. It is bilateral in 20% of the cases. Most often it appears due to severe occlusion of the carotid arteries (ICA, MCA>ECA), described in 1963 by Kearns and Hollenhorst. Occasionally it can be determined by the obstruction of ophtalmic artery or some arterities (Takayasu, giant cell arteritis). The risk factors are: age between 50-80 years, males (M:F = 2:1), arterial hypertension, diabetes, coronary diseases (5% of the cases develop ocular ischemic syndrome), vascular stroke, hemodialysis. The case we present is of an 63 years old man known with primary arterial hypertension, hypercholesterolemia, diabetes type 2 non insulin dependent and diagnosticated with ischemic cerebral stroke and bilateral obstruction of internal carotid arteries in march 2010, who is presenting for visual impairment in both eyes. The imaging investigations show important carotid occlusion and at the ophthalmologic evaluation there are ocular hypertension and rubeosis iridis at the right eye, optic atrophy at both eyes (complete in the right eye and partial in the left eye), with superior altitudinal visual field defect in left eye. The following diagnosis was established: Chronic ocular ischemic syndrome in both eyes with Neovascular glaucoma at the right eye, Anterior ischemic optic neuropathy at the left eye and laser panphotocoagulation at the right eye was started.

[Alternative therapeutic excision of intraepithelial conjunctival carcinoma with corneal extension]. / Alternative terapeutice la excizia unui carcinom intraepitelial conjunctival cu extensie corneeana.

Surgical treatment for conjunctival neoplasms, with wide local excision, with or without supplemental cryotherapy to the surgical margins represents the treatment of choice for this pathology. In some cases, these neoplasms can be diffuse or multifocal, with borders that are difficult to detect clinically, such that topical therapies offer a more efficient method for treating the entire ocular surface, delivering high drug concentrations at this level, with negligible systemic side effects. Beginning from the clinical case of a patient diagnosed with conjunctival intraepithelial neoplasia, we try to present other therapeutical alternatives, although in this case the therapeutical approach was the classic one.