Raffaele Nuzzi

Conjunctiva and subconjunctival tissue in primary open-angle glaucoma after long-term topical treatment: an immunohistochemical and ultrastructural study

Abstract• Background: Primary open-angle glaucoma is commonly treated with long-term hypotensive medical therapy. When this approach becomes inadequate, therapy proceeds with surgery. The present study investigates morphological changes in the conjunctival and subconjunctival tissues induced by short- and long-term topical medical therapy of primary open-angle glaucoma. • Methods: Comparisons were made between biopsy specimens from glaucomatous patients, who received specific eyedrop therapy (timolol and pilocarpine) for various periods of time, and control patients with no conjunctival pathology or topical treatment. Histological, immunohistochemical and ultrastructural parameters were investigated. • Results: The morphometric analysis of histological sections and immunohistochemistry (anti-fibronectin antibody) in medium-and long-term therapy patients showed: (a) significant increases in the thickness and number of epithelial cell layers; (b) significant increases in the fibroblast density in both subepithelial and deep connective tissue; and (c) a more compact connective tissue, richer in collagen fibers arranged in whirls, with some inflammatory elements. These findings were confirmed by the ultrastructural analysis. In the same patients, the other immunohistochemical parameters investigated (anti-HLA-DR, anti-CD1a, anti-CD4, anti-CD8, anti-IL2 and C3b antibodies) revealed a tendency to chronic inflammation. Following specific surgery, this tendency manifested itself in a diffuse immune response, especially in those patients who underwent medium-and long-term medical therapy. • Conclusion: According to these results, antiglaucomatous surgery should be rehabilitated and considered as an alternative to long-term medical therapy in the first-instance treatment of primary open-angle glaucoma.

Local and Systemic Complications after Intravitreal Administration of Anti-Vascular Endothelial Growth Factor Agents in the Treatment of Different Ocular Diseases: A Five-Year Retrospective Study

Abstract Purpose: To observe the frequency of complications in patients undergoing intravitreal anti-VEGF injections for different ocular diseases in a five-year period. Materials and Methods: Charts of patients receiving intravitreal anti-VEGF were retrospectively reviewed. Out of 1173 eyes, 762 were treated with bevacizumab, 382 with ranibizumab, and 29 with pegaptanib. Data recorded included demographic information, clinical findings, total injections received, and info about the onset of adverse effects. Results: 12.86% of the eyes treated with bevacizumab presented side-effects, while ratings in the ranibizumab and pegaptanib groups were 15.97% and 20.69%, respectively. Odds ratios calculated comparing incidences after each anti-VEGF are 0.78 (bevacizumab versus ranibizumab, p = 0.152), 0.57 (bevacizumab versus pegaptanib, p = 0.227), and 0.73 (ranibizumab versus pegaptanib, p = 0.508). A total of 185 complications were detected (62.16% after bevacizumab). Ocular side-effects registered were 40 cases of sustained intraocular pression (IOP) elevation, one infectious uveitis, one retinal detachment, and one sub-retinal hemorrhage. Other cases were related to transient IOP elevation immediately after injection. Systemic complications registered were one case of nausea, one episode of chest pain with acute vision loss, and one case of acute blood hypertension. Conclusions: The majority of significant complications occurred in patients receiving multiple bevacizumab administrations. However, results may be affected by the difference in the utilization amount for each drug. AMD patients were the most represented, probably due to greater indication to treatment.

Fluorescence histochemical demonstration of adrenergic terminations in the human choroid.

With the existing literature on the aspects of anatomic and physiological ocular choroid membrane variables in mind, the authors verify the possibility of applying the methods of Axelsson et al and of Lindvall and Bjorklund, as simplified by Furness and Costa for fluorescent microscopy, to the study of human choroid nerve topographic distribution. The material for the study was obtained from three human eyeballs, two enucleated because of malignant melanoma of the choroid and one because of neoplasia of the ciliary body. A binocular dissecting microscope was used. A fluorescent microscope was used to observe the histological specimens and photographs were taken. The following results are presented and discussed: 1) the fluorescent paravascular nervous fibres and periarterial nervous plexuses divided into preterminal and terminal fibres; 2) in the suprachoroidal layer, there were small groups of polygonal nervous branches with or without this connection; 3) the most intervasal plexus development was in the posterior part of the vascular layer with preterminal and terminal fibres, 4) in the intervascular space, melanocytes and free adrenergic nervous terminations were observed; 5) adrenergic fibres were not observed in the choriocapillaris of the choroid membrane; 6) there were adrenergic neurons in the vascular layer.

Ocular Complications in Laparoscopic Surgery: Review of Existing Literature and Possible Prevention and Treatment

ABSTRACT During laparoscopic surgery, ocular complications are possible, sometimes leading to devastating visual losses, hardly susceptible to recovery, although rare. Principal ocular adverse events are represented by corneal abrasions and the perioperative visual loss (POVL). POVL onset is related to intraocular pressure elevations (particularly after patient positioning in Trendelenburg or prone decubitus, depending on the surgical procedure), anesthesiologic factors and patients’ characteristics. In the light of evidence from the existing literature, the authors suggest surgical and anesthesiologic measures to prevent and manage ocular complications in laparoscopic surgery. Apart from general recommendations, this article indicates practical guidelines specific for robot-assisted laparoscopic interventions and spinal surgery, as well as laparoscopic colorectal resection, radical prostatectomy, and gynecologic surgery. In conclusion, in order to better manage these complications, it is advisable to develop an interdisciplinary collaboration between surgeons, anesthesiologists, and ophthalmologists, on a procedural and medico-legal level, with the intent of mutual training.

Gd accumulation in tissues of healthy mice upon repeated administrations of Gadodiamide and Gadoteridol

The aim of this work was to investigate, by five different administration protocols, the impact of the dosage, the time passed after the last injection and the frequency of injections, on accumulation and distribution of Gd-containing species in the body tissues of healthy mice upon repeated injections of Gadolinium Based Contrast Agents (GBCAs). Gadodiamide and Gadoteridol have been compared. The amount of Gd retained in several tissues/organs (cerebrum, cerebellum, spleen, liver, kidneys, eyes, skin, bone and muscle) has been assessed by ICP-MS upon administration of the GBCAs i) at three weeks or three months after the last administration, ii) when one, three or twelve doses of GBCA were administered and iii) when administrations were made every two weeks. Gd was found in all tissues after the administration of Gadodiamide. Conversely, in the case of Gadoteridol, Gd was detected only in spleen, kidneys, liver and bone. The amounts of Gd found in spleen, liver and kidneys markedly decrease upon increasing the time that has passed after the last administration, whereas, in the case of Gadodiamide, the decrease of Gd found in bone, cerebrum and cerebellum appears to occur at a much slower rate. Overall, areas of long term deposition appear to be bone and spleen for both GBCAs. In conclusion, our findings demonstrate that intravenous multiple administrations of GBCAs is associated with extensive multiorgan retention which is reduced but not eliminated by the use of the macrocyclic Gadoteridol as well as by adopting reduced and/or less frequent dosing.

Glaucoma: Biological Trabecular and Neuroretinal Pathology with Perspectives of Therapy Innovation and Preventive Diagnosis

Glaucoma is a common degenerative disease affecting retinal ganglion cells (RGC) and optic nerve axons, with progressive and chronic course. It is one of the most important reasons of social blindness in industrialized countries. Glaucoma can lead to the development of irreversible visual field loss, if not treated. Diagnosis may be difficult due to lack of symptoms in early stages of disease. In many cases, when patients arrive at clinical evaluation, a severe neuronal damage may have already occurred. In recent years, newer perspective in glaucoma treatment have emerged. The current research is focusing on finding newer drugs and associations or better delivery systems in order to improve the pharmacological treatment and patient compliance. Moreover, the application of various stem cell types with restorative and neuroprotective intent may be found appealing (intravitreal autologous cellular therapy). Advances are made also in terms of parasurgical treatment, characterized by various laser types and techniques. Moreover, recent research has led to the development of central and peripheral retinal rehabilitation (featuring residing cells reactivation and replacement of defective elements), as well as innovations in diagnosis through more specific and refined methods and inexpensive tests.

Use of Intravitreal Dexamethasone in a Case of Anterior Ischemic Optic Neuropathy

Nowadays there is no unique and well-established treatment for nonarteritic anterior ischemic optic neuropathy, despite being the main acute pathology that affects the optic nerve in the elderly population and often resulting in a significant loss of visual acuity. The effectiveness of oral steroids is still under debate in the international literature, although many studies show that patients treated with high doses of systemic corticosteroids have a significantly higher chance of improved visual acuity and visual fields. The authors propose an intravitreal dexamethasone injection/implant as initial and acute therapy. Compared to systemic corticosteroids, intravitreal dexamethasone has the advantage of avoiding any systemic side effects of steroids. On the other hand, a rise in intraocular pressure might occur, manageable with local antiglaucoma drugs, especially in patients at risk, and there is a risk of induced cataract. The pharmacodynamics of the intravitreal dexamethasone slow-release implant is characterized by a first step with high release concentrations and a second following phase with decreasing concentrations. Therefore, the use of emergency dexamethasone (high concentration) intravitreal injection is justified as a treatment after the first detection of an ischemic optic anterior neuropathy.

Complications of Intravitreal Anti-VEGF Drugs: A Report on Our Personal Experience

Intravitreal anti-vascular endothelial growth factor (VEGF) agents usage is widely spread as primary treatment of many vitreo-retinal disease such as neovascular age-related macular degeneration, diabetic macular edema, macular edema secondary to retinal vein occlusion and other conditions. Recently we conducted a five year retrospective chart analysis of patients that arrived at the Macular Disease Center of our institute in order to assess the frequency of local and systemic complication in patients undergoing intravitreal bevacizumab, ranibizumab and/or pegaptanib for the treatment of different ocular diseases [1].

Ophthalmic evaluation and management of traumatic accidents associated with retinal breaks and detachment: a retrospective study.

Purpose This retrospective study reviews a group of patients with retinal breaks or retinal detachment following ocular trauma. Methods A total of 94 patients were included in the study. They underwent closed globe injuries causing multiple retinal breaks or retinal detachment at time of presentation in the emergency department. Analysis concerned epidemiologic, clinical, and therapeutic aspects, both in short-term (1 and 3 months) and long-term (6-12 months) follow-up. Results A total of 85% of patients were male, involved in work-related injuries, and complaining visual function decrease. Retinal breaks were mostly singular, U-shaped, and located in the upper temporal quadrant. At presentation, visual acuity ≥5/10 and Ocular Trauma Score of 4 were the most represented. Fifty-eight patients (61.70%) underwent repair within 48 hours of the trauma, 27 (28.73%) within 7 days, and 9 (9.57%) more than 7 days after trauma. Procedures performed were photocoagulation with argon laser (52%), episcleral buckle (34.45%), or vitrectomy associated with episcleral buckle and intraoperative argon laser (13.55%). A total of 92% of patients treated within 48 hours had better or unchanged visual acuity in 6-12 months of follow-up. All patients treated more than 7 days after trauma had worse visual acuity (p<0.01 with Student t test). Conclusions Detailed clinical history, well-done preoperative examination, early diagnosis, and prompt parasurgical or surgical repair are significant prognostic factors for better visual outcome and lower incidence of relapse.

Best Prophylactic Strategy in Groups at Risk of Intraoperative Floppy Iris Syndrome Development: Comparison Between Atropine Instillation and Adrenaline Intracameral Injection

Background: Intraoperative Floppy Iris Syndrome (IFIS) is an important cause of surgical complications and iris defects in patients undergoing phacoemulsification that were treated with selective subtype α1A receptor antagonists for a long period of time. To date, no definitive preventive strategy has emerged, yet. The need of prophylaxis is dictated by the high prevalence of males affected by benign prostatic hyperplasia undergoing cataract surgery. Objective: To identify the best prophylactic strategy in groups at risk of IFIS development by comparing two mydriatic treatments in course of phacoemulsification surgery. Methods: 81 eyes of 81 patients in treatment with Tamsulosin were enrolled in the study. 43 eyes were treated with atropine sulfate 1% while 38 eyes received an injection of mydriatic solution containing epinephrine in the anterior chamber. All phacoemulsifications were videotaped in order to assess the occurrence of IFIS and the severity of the syndrome. Results: The treatment group showed a statistically significant reduction (p = 0.0115) of floppy iris syndrome incidence, from 86.05% (37/43) of the atropine group to 60.53% (23/38). The analysis showed a reduction of IFIS mild form only, whereas the incidence of severe forms remained unchanged. Conclusions: We believe that IFIS may arise through two different mechanisms: pharmacological antagonism and anatomical modifications. Patients suffering from mild forms of the disease showed a statistically significant reduction of IFIS incidence after intraoperative prophylaxis due to epinephrine’s ability to displace Tamsulosin, resulting in the increase of iris tone when the disease is caused mainly by receptorial antagonism. On the contrary, prophylaxis does not deliver any valuable result in case of severe forms where the anatomical variations play a major role.