Corneal Damage Research Articles

Layer-by-layer oral-deliverable nanoparticles targeted microfold cells to promote lutein absorption in alleviating dry eye disease

Bioactive compound intervention of dry eye disease has been considered as a promising approach due to the lower adverse reactions. In this study, layer-by-layer oral-deliverable lutein nanoparticles targeted to microfold cells in the intestinal Peyer's patches through the specific interaction between yeast β-glucan and receptor dectin-1 were designed and prepared using phycocyanin, chitosan and 3-boronobenzoic acid modified yeast β-glucan as carriers in alleviating dry eye disease. In vitro studies confirmed that the dectin-1 specific lutein nanoparticles could specifically target microfold cells from Peyer's patches of the intestine, which significantly inhibited the reactive oxygen species elevation and mitochondrial membrane potential reduction produced by oxidative stress and inflammation. Pharmacokinetic results showed that the bioavailability of lutein in plasma and eyeballs was increased by 2.63 and 1.81 times by oral administration of lutein nanoparticles. The lutein nanoparticles could effectively relieve dry eye disease by alleviating corneal damage, restoring tear film homeostasis and reducing corneal keratinization in Balb/c mice. The oral deliverable dectin-1 specific lutein nanoparticles constructed in this study provided potential application for improving bioavailability of hydrophobic nutrients during the intervention of dry eye diseases.

Effect of mitomycin C and 5-fluorouracil on wound healing in patients undergoing glaucoma surgery: A meta-analysis.

Increased intraocular pressure (IOP) is a risk factor for glaucoma. One treatment option is trabeculectomy. Antimetabolic agents are used in the operation to decrease the post-operative scarring of the wound. The two most common medicines are Mitomycin C (MMC) and 5-Fluorouracil (5-FU). The aim of this research is to assess the effect of MMC on post-operation wound healing in comparison with 5-FU in addition to trabeculectomy. Well, we went through four common databases. Our language was limited to English during the study. The last time we looked at the e-databases was August 2023. Case control studies were performed where MMC resulted in better wound healing than 5-FU. Researchers selected a total of 1023 trials and eventually selected six trials for data analysis. Four hundred and ninety one cases of glaucoma were treated with trabeculectomy. Among them, 246 were given MMC and 245 were given 5-FU during operation. Six trials showed that there was no statistical difference between MMC and 5-FU in the incidence of post-operative wound leak in glaucoma patients who received trabeculectomy (OR, 1.21; 95% CI, 0.63-2.30 p = 0.57); Five trials demonstrated that MMC was associated with a reduced risk of post-operative corneal damage compared to 5-FU injection (OR, 0.18; 95% CI, 0.06-0.56 p = 0.003); In both trials, the incidence of post-operative bleeding was not significantly different from that of 5-FU injected in the MMC group (OR, 0.33; 95% CI, 0.05-2.16 p = 0.25). Our results indicate that MMC is superior to 5-FU in the reduction of post-operative corneal injury. Additional comparisons between MMC and 5-FU are required in order to increase the reliability and effectiveness of these findings.

A Novel Combination Therapy Tβ4/VIP Protects against Hyperglycemia-Induced Changes in Human Corneal Epithelial Cells.

Despite the prevalence of diabetic retinopathy, the majority of adult diabetic patients develop visually debilitating corneal complications, including impaired wound healing. Unfortunately, there is limited treatment for diabetes-induced corneal damage. The current project investigates a novel, peptide-based combination therapy, thymosin beta-4 and vasoactive intestinal peptide (Tβ4/VIP), against high-glucose-induced damage to the corneal epithelium. Electric cell-substrate impedance sensing (ECIS) was used for real-time monitoring of barrier function and wound healing of human corneal epithelial cells maintained in either normal glucose (5 mM) or high glucose (25 mM) ± Tβ4 (0.1%) and VIP (5 nM). Barrier integrity was assessed by resistance, impedance, and capacitance measurements. For the wound healing assay, cell migration was also monitored. Corneal epithelial tight junction proteins (ZO-1, ZO-2, occludin, and claudin-1) were assessed to confirm our findings. Barrier integrity and wound healing were significantly impaired under high-glucose conditions. However, barrier function and cell migration significantly improved with Tβ4/VIP treatment. These findings were supported by high-glucose-induced downregulation of tight junction proteins that were effectively maintained similar to normal levels when treated with Tβ4/VIP. These results strongly support the premise that Tβ4 and VIP work synergistically to protect corneal epithelial cells against hyperglycemia-induced damage. In addition, this work highlights the potential for significant translational impact regarding the treatment of diabetic patients and associated complications of the cornea.

In vitro validation: GLY alleviates UV-induced corneal epithelial damage through the HMGB1-TLR/MyD88-NF-κB signaling pathway

UV-induced corneal damage is a common ocular surface injury that usually leads to corneal lesions causing persistent inflammation. High mobility group box 1 (HMGB1) is identified as an inflammatory alarm in various tissue injuries. Here, this study first evaluates the repair effect of the HMGB1-selective inhibitor GLY in UV-induced corneal damage; Secondly, the inhibitory effect of GLY on UV-induced corneal damage induced inflammation and the potential therapeutic mechanism of GLY were studied. GLY effectively attenuates the expression of UV-induced inflammatory factors and HMGB1, TLR/MyD88, NF-κB signaling pathway genes at the mRNA and protein levels. In addition, RT-PCR and Western Blot experiments after knocking down HMGB1 and TLR2/9 genes showed that GLY alleviated corneal inflammation by inhibiting the HMGB1-TLR/MyD88 signaling pathway. The results of this study show that targeting HMGB1-NF-κB by GLY can alleviate the inflammatory response induced by UV induction.

Update on gene therapies in pediatric ophthalmology

Rare eye diseases encompass a broad spectrum of genetic anomalies with or without additional extraocular manifestations. Genetic eye disorders in pediatric patients often lead to severe visual impairments. Therefore, a challenge of gene therapy is to provide better vision to these affected children. In recent years, inherited retinal diseases, inherited optic neuropathies, and corneal dystrophies have dominated discussions to establish gene and cell replacement therapies for these diseases. Gene therapy involves the transfer of genetic material to remove, replace, repair, or introduce a gene, or to overexpress a protein, whose activity would have a therapeutic impact. For the majority of anterior segment diseases, these studies are still emerging at a preclinical stage; however, for inherited retinal disorders, translation has been reached, leading to the introduction of the first gene therapies into clinical practice. In the past decade, the first gene therapy for biallelic RPE65-mediated inherited retinal dystrophy has been developed and the FDA and EMA both approved ocular gene therapy. Other promising approaches by intravitreal injection have been investigated such as in CEP290-Leber congenital amaurosis. Various techniques of gene therapies include gene supplementation, CRISPR-based genome editing, as well as RNA modulation and optogenetics. Optogenetic therapies deliver light-activated ion channels to surviving retinal cell types in order to restore photosensitivity. Beyond retinal function, ataluren, a nonsense mutation suppression therapy, enables ribosomal read-through of mRNA containing premature termination codons, resulting in the production of a full-length protein. An ophthalmic formulation was recently evaluated with the aim of repairing corneal damage, pending new clinical studies. However, various congenital disorders exhibit severe developmental defects or cell loss at birth, limiting the potential for viral gene therapy. Therefore mutation-independent strategies seem promising for maintaining the survival of photoreceptors or for restoring visual function. Restoring vision in children with gene therapy continues to be a challenge in ophthalmology. © 2023 Published by Elsevier Masson SAS on behalf of French Society of Pediatrics.

Fluorescein Staining in an Autoimmune Dry Eye Rat Model to Examine Corneal Damage

Fluorescein Staining in an Autoimmune Dry Eye Rat Model to Examine Corneal Damage

Fluorescein Staining in an Autoimmune Dry Eye Rat Model to Examine Corneal Damage

Fluorescein Staining in an Autoimmune Dry Eye Rat Model to Examine Corneal Damage

Association between Corneal Higher-Order Aberrations Evaluated with a Videokeratographer and Corneal Surface Abnormalities in Dry Eye.

Analysis of higher-order aberrations (HOAs) is one reported method for evaluating dry eye disease (DED)-related loss of visual function. Tear film (TF) instability and corneal epithelial damage (CED) are both reportedly responsible for HOAs in DED, although, to the best of our knowledge, there are no reported methods that allow concurrent evaluation of their effects. In this study, we used a videokeratographer (VK) to continuously measure HOAs in DED after eye opening and investigated factors of ocular surface abnormalities that determine HOAs. This study involved 96 DED cases that underwent DED symptom assessment with a questionnaire and examination of tear volume, TF abnormalities (i.e., TF lipid-layer interference grades and spreading grades, and non-invasive breakup time and fluorescein breakup time), and CED, and their correlation with HOAs evaluated via VK. The results show that HOAs at 1 or 2 s after eye opening can reflect TF instability and CED within the central 4-millimeter-diameter area of the optical zone in DED eyes concurrently. This finding may be useful for the rapid and non-invasive detection and evaluation of degraded visual function in DED cases with a variety of clinical features.

Emerging Strategies in Treating Corneal Alkali Burns: A Narrative Review.

Corneal alkali burns represent a complex and debilitating ocular injury, necessitating innovative strategies for effective management. This narrative medical review seeks to provide a comprehensive exploration of emerging approaches in the treatment of corneal alkali burns. The primary objectives of this review are multifaceted. First, we aim to unravel the intricate pathophysiology of corneal alkali burns, delving into the immediate and long-term consequences of alkali exposure on ocular tissues. Understanding the underlying mechanisms, including oxidative stress, inflammation, and neovascularization, is essential for the development of targeted therapeutic interventions. Second, we assess the efficacy of novel treatment modalities, encompassing pharmacological agents and surgical techniques, with a focus on their ability to mitigate corneal damage, facilitate tissue regeneration, and preserve visual function. By analyzing the latest clinical findings, we aim to identify promising avenues for improved patient outcomes. Temporal dynamics play a crucial role in the healing process, and thus our review investigates the progression of corneal lymphangiogenesis and the expression patterns of key growth factors, such as vascular endothelial growth factor-C (VEGF-C). These insights into the timing of corneal healing provide valuable guidance for tailoring therapeutic interventions to specific stages of injury. Finally, we delve into regenerative therapies, particularly the potential of mesenchymal stem cells (MSCs) and their secretome as anti-inflammatory and antiangiogenic agents. By summarizing the promising results from preclinical and clinical studies, we illuminate the prospects of regenerative approaches in corneal alkali burn management. This narrative review aspires to serve as an indispensable resource for clinicians, researchers, and healthcare professionals involved in the treatment of corneal alkali burns. By addressing these objectives, we aim to foster a deeper understanding of this challenging condition, facilitate the development of innovative strategies, and ultimately enhance patient outcomes in the realm of corneal health and vision preservation.

A20 ameliorates Aspergillus fumigatus keratitis by promoting autophagy and inhibiting NF-κB signaling

Fungal keratitis (FK) is a serious, potentially sight-threatening corneal infection, which is associated with poor prognosis. A20, also called TNFAIP3, plays significant roles in the negative regulation of inflammation and immunity. However, the function of A20 in Aspergillus fumigatus (A. fumigatus) keratitis remains obscure. Herein, we found that the level of A20 is increased in human corneal epithelial cells (HCECs) and in mouse corneas with A. fumigatus infection, and that nuclear factor-κB (NF-κB) signaling is required for A20 upregulation. A20 overexpression inhibits A. fumigatus-mediated inflammatory responses, while A20 knockdown results in opposite effect. Mechanically, we showed that A20 inhibits NF-κB signaling and activates autophagy in infected HCECs. We also showed that inhibition of NF-κB signaling reverses the increased inflammatory responses in infected HCECs with A20 knockdown. Furthermore, autophagy blockage impedes the anti-inflammatory effect of A20 in A. fumigatus infected HCECs. Moreover, A20 ameliorates the corneal damage and inflammation in A. fumigatus infected mouse corneas. In conclusion, this study reveals that A20 alleviates A. fumigatus keratitis by activating autophagy and inhibiting NF-κB signaling. This suggests that exogenous use of A20 protein may be a potentially promising therapeutic strategy for FK treatment.

Conjunctival, Scleral and Corneal Complications in Vitreoretinal Surgery

Vitreoretinal surgery has been associated with corneal, conjunctival and scleral complications. These complications may cover corneal epithelial and endothelial cells damage (epithelial defects, neurotrophic and band keratopathy, refractive error changes, corneal decompansation etc.), ocular surface disease, early hypotonia, diplopia, strabismus, subconjunctival silicone oil, episcleral pigmentation, infection and inflammation etc. Risk factors may include a history of the previous ocular surgery, aphakia and pseudophakia, prolonged duration of surgery, intraoperative epithelial debridement, intraoperative lensectomy, diabetic patients, use of adjunctive intraocular long-acting expansile gases or silicone oil, use of scleral buckling, sutureless sclerotomy incisions etc. These complications should be known and noticed due to affect visual outcomes and healing of patients. Corneal, conjunctival and scleral complications are summarized in this article.

Multi-Target Effect of Aloeresin-A against Bacterial and Host Inflammatory Targets Benefits Contact Lens-Related Keratitis: A Multi-Omics and Quantum Chemical Investigation.

Contact lens-mediated microbial keratitis caused by Pseudomonas aeruginosa and Streptococcus pneumoniae provokes corneal damage and vision loss. Recently, natural phytochemicals have become complementary medicines for corneal destruction. Herein, we aimed to identify multi-targeting Aloe vera-derived phytochemicals capable of inhibiting bacterial and host targets of keratitis through ADME (absorption, distribution, metabolism, and excretion), docking, molecular dynamics (MD) simulation, MMGBSA (molecular mechanics generalized Born surface area) and density functional theory (DFT) investigations. An extensive literature search revealed ExoU, ExoS, ExoT, ExoY, and PLY as virulent bacterial targets. Simultaneously, differential gene expression (DGE) and pathway enrichment analysis-specified host transcription factor (SPI1) influences keratitis pathogenesis. Molecular docking analysis uncovered aloeresin-A as a promising inhibitor against bacterial and host targets, demonstrating strong binding energies ranging from -7.59 to -6.20 kcal/mol. Further, MMGBSA and MD simulation analysis reflect higher binding free energies and stable interactions of aloeresin-A with the targets. In addition, DFT studies reveal the chemical reactiveness of aloeresin-A through quantum chemical calculations. Hence, our findings show aloeresin-A to be a promising candidate for effectively inhibiting keratitis. However, additional research is imperative for potential integration into lens care solutions.

Intraocular pressure measurement method using acoustic signals

Glaucoma can cause blindness, and one of the main causes has been found to be compression of the optic nerve by high intraocular pressure (IOP). In glaucoma, IOP is the most important biomarker for disease diagnosis, treatment, and monitoring. Among methods designed to measure IOP, direct contact with the eyeball is the most commonly used method due to its high accuracy. However, this method requires the intervention of a medical staff, and has problems, such as infection, fear, and corneal damage, which occur when the patient's IOP is measured. Therefore, in this study, while overcoming these problems, we intend to present a new IOP measurement method that inherits the advantages of the existing method. The eyeball has a structure in which body fluid is contained in an outer shell of viscoelastic material, and the change in pressure applied to the outer skin according to the inflow of body fluid appears as IOP. When an acoustic signal is emitted to an eyeball with a different IOP, the wave propagation characteristics vary depending on the composition of the body fluid, and the IOP is estimated. It is expected that the patient can directly measure and manage IOP using the proposed method.

A Multicenter Prospective Randomized Controlled Study of a New Corneal Wetting Agent During Ophthalmologic Surgery.

A multicenter prospective randomized controlled study was used to investigate the effect and safety of a new corneal wetting agent called the Corneal Surface Viscoelastic Protector (CsVisc, Success Bio-Tech Co., Ltd, China), on the corneal epithelium during ophthalmic surgery by comparison with the commercially available Cornea Protect (CP, Valeant Med Sp. zo. o. Leobendorf, Austria). This multicenter prospective randomized controlled study comprised patients scheduled for cataract surgery and pars plana vitrectomy. The patients were randomly assigned to receive either a new corneal wetting agent (CsVisc) or Cornea Protect (CP, Valeant Med Sp. zo. o. Leobendorf, Austria). Optical clarity during surgery, application frequency, duration of effect, diffusion time of corneal wetting agents, fluorescein staining, intraocular pressure (IOP), tear-film break-up time (TBUT), and Schirmer I test (SIT) were assessed. Adverse events were noted on the designated patient case report forms. A total of 149 eyes (149 patients, mean age 62years; range 25-80years) were included in the study. There were 74 eyes in the control group and 75 eyes in the study group. In patients who underwent vitrectomy, the frequency of application was 1.62 ± 1.03 in the study group and 1.39 ± 0.66 in the control group, with no significant difference (P = 0.399), and the duration of effect was 19.16 ± 6.94min in the study group and 19.06 ± 7.22min in the control group, with no significant difference (P = 0.835). The optical clarity of the study group was not significantly different from that of the control group (P = 0.485). In patients who underwent cataract surgery, the frequency of application was 1.10 ± 0.38 in the study group and 1.07 ± 0.26 in the control group, and the difference was not significant (P = 0.950). The difference between the duration of effect in the study group (8.32 ± 2.50min) and the control group (7.63 ± 2.52min) was not significant (P = 0.310). The difference in optical clarity scores between the two groups was not statistically significant (P = 0.600). Among all patients in this study, the diffusion time of the corneal wetting agent was 14.97 ± 10.07s in the control group and 11.23 ± 8.41s in the study group, with a statistically significant difference (p = 0.008). The frequency of adverse events was 20.00% (15/75) in the study group and 14.86% (11/74) in the control group, with no statistically significant difference (P = 0.409). There were no serious adverse events related to the test medical device or causing patients to withdraw from the study. The CsVisc is safe and effective in preventing intraoperative corneal epithelial damage due to corneal dryness and can be comparable to the CP. In addition, the CsVisc has a shorter diffusion time.

Chemical Burn Injury on the Cornea Following Skin Preparation With Chlorhexidine in Tonsillectomy and Adenoidectomy.

This article report discusses a pediatric patient who suffered a corneal chemical burn injury after tonsillectomy and adenoidectomy surgery due to skin preparation with chlorhexidine. In this case, inadequate sealing of the eye shield during skin preparation allowed the chlorhexidine-alcohol solution to accumulate at its edge and gradually penetrate, resulting in the corneal injury. Prompt ophthalmological intervention and appropriate eye care treatment led to a gradual improvement in the patient's symptoms. The authors aim to present the case, share the revisions made to our skin preparation policy, and emphasize the importance of cautious antiseptic use to minimize the risk of adverse events. Adverse effects of chlorhexidine, such as hypersensitivity reactions and burns, including corneal damage, are highlighted. Health care providers should exercise caution when selecting and applying antiseptics, considering patient-specific factors, and comprehensive training should be provided to promote adherence to safe antiseptic practices during surgical procedures.

Topical formulations of Aprepitant are safe and effective in relieving pain and inflammation, and drive neural regeneration

PurposeTo test long-term ocular toxicity and analgesic/anti-inflammatory efficacy of two novel ocular formulations of neurokinin 1 receptor (NK1R) antagonist Aprepitant. Methodsfor toxicity studies, two Aprepitant formulations (X and Y) were tested on C57BL/6 N mice. Gold standards were 0.4% Oxybuprocaine, 0.1% Diclofenac, or saline. For efficacy studies, C57BL/6 N mice underwent corneal alkali burn, and then received Aprepitant formulation X, Dexamethasone or saline. Eye-drops were applied 3 times/day for 90 days (toxicity) and 14 days (efficacy). Stromal opacity, corneal epithelial damage, nociception and sensitivity were assessed in vivo. The eye-wiping test and corneal sensitivity were assessed to evaluate analgesic efficacy and nerve function. At the end of the experiments mice were euthanized, and corneas were dissected for immunohistochemistry and RT-PCR analyses. ResultsIn normal mice, formulation X was not toxic when topically administered for 90 days. Formulation Y was associated with increased leukocyte infiltration in the cornea (p < 0.001). X1 and X2 formulations significantly reduced corneal pain, as Diclofenac and Oxybuprocaine, but did not reduce corneal sensitivity. Formulation Y, instead, was not analgesic at any time point. In the alkali burn model, X1 and X2 formulation enhanced epithelial damage recovery, and reduced inflammation both at day 7 and 14. Moreover, formulation X showed a stronger analgesic effect when compared to the saline and Dexamethasone groups (p < 0.01). Finally, formulation X1 and X2 restored corneal sensitivity by promoting corneal nerve regeneration. ConclusionsAprepitant X formulation is a promising candidate for the treatment of pain associated with inflammation of the ocular surface.

Effect of epigallocatechin gallate (EGCG) on neutrophils count and interleukin-6 (IL-6) expression in Pseudomonas aeruginosa keratitis: an experimental study on Rattus norvegicus rat

Link of Video Abstract: https://youtu.be/pCACVaojEVMBackground: Pseudomonas aeruginosa keratitis is a prevalent ocular illness that carries the potential risk of endophthalmitis and corneal perforation. The use of antibiotics effectively eradicates the bacteria; nevertheless, the corneal damage caused by toxins remains unresolved, resulting in the thinning of the cornea, which can ultimately lead to corneal perforation or the development of corneal fibrosis. This study aims to analyze the quantification of neutrophils and the expression levels of interleukin-6 in the Pseudomonas aeruginosa keratitis model. Methods: The study used an experimental research design. The research utilized a Rattus norvegicus corneal preparation to establish a keratitis model. Each test group consisted of six samples, including a negative control (solvent), moxifloxacin 0.5%, and a combination of moxifloxacin 0.5% and EGCG at a concentration of 50 µg/mL. Results: The combined group of 0.5% moxifloxacin and epigallocatechin gallate (EGCG) 50 µg/mL exhibited a reduced count of neutrophils compared to the group treated with 0.5% moxifloxacin alone. The findings indicated a statistically significant disparity in the neutrophil count across the various treatment groups (p&lt;0.05). No significant distinction was observed in the neutrophil count between the moxifloxacin 0.5% group and the combination group (p&gt;0.05). The average percentage of IL-6 expression level in the group treated with a combination of 0.5% moxifloxacin and 50 µg/mL EGCG was found to be lower compared to the group treated with only 0.5% moxifloxacin. There was statistically significant variation in the expression of IL-6 across the three treatment groups (p&lt;0.05). There was no statistically significant difference in the level of IL-6 expression between the moxifloxacin 0.5% group and the combination group (p&gt;0.05). Conclusion: The results of this investigation demonstrated that EGCG possesses the capability to serve as an adjunct treatment for the suppression of inflammation in cases of Pseudomonas aeruginosa keratitis.

Corneal damage threshold induced by supercontinuum source: A further study.

Previous report shows that corneal spot size is an important influence factor on damage threshold induced by supercontinumm (SC) source. However, damage thresholds were determined for the spot size of only 0.37 mm due to the low output of the employed SC source at that time. The objectives of this study are to determine the lowest possible corneal damage threshold at a large corneal spot size using a more powerful SC source and provide data for the future possible refinements of laser safety standards. A series of experiments was conducted in the New Zealand white rabbit model to determine the corneal damage threshold induced by a 900-2000 nm SC source, with corneal 1/e beam diameter of about 1.2 mm. Slit-lamp biomicroscope was employed to reveal the corneal damage characteristics. By employing the action spectra determined through the analysis of current laser safety guidelines and standards, the effective damage threshold could be calculated. The determined damage threshold given in terms of the peak radiant exposure for the exposure duration of 0.14 s was 44.3 J/cm2 . At threshold level, corneal damages involved the epithelium and the shallower stroma. The safety factor between the effective damage threshold and the corresponding maximum permissible exposure (MPE) was about 45. Present corneal MPEs in the wavelength range of 700-1200 nm may be conservative and corneal damage thresholds for the infrared A wavelengths should be determined in future studies.

An Ex Vivo Pilot Study to Assess the Feasibility of 3D Printing of Orbital Implants in Horses.

Severe ophthalmic conditions such as trauma, uveitis, corneal damage, or neoplasia can lead to eye removal surgery. Poor cosmetic appearance resulting from the sunken orbit ensues. The aim of this study was to demonstrate the feasibility of manufacturing a custom-made 3D-printed orbital implant made of biocompatible material for the enucleated horse and usable in conjunction to a corneoscleral shell. Blender, a 3D-image software, was used for prototype design. Twelve cadaver heads of adult Warmbloods were collected from the slaughterhouse. On each head, one eye was removed via a modified transconjunctival enucleation while the contralateral eye was kept intact as control. Ocular measurements were collected on each enucleated eye with the help of a caliper and used for prototype sizing. Twelve custom-made biocompatible porous prototypes were 3D-printed in BioMed Clear resin using the stereolithography technique. Each implant was fixated into the corresponding orbit, within the Tenon capsule and conjunctiva. Heads were frozen and thin slices were then cut in the transverse plane. A scoring system based on four criteria (space for ocular prosthesis, soft-tissue-coverage, symmetry to the septum, and horizontal symmetry), ranging from A (proper fixation) to C (poor fixation), was developed to evaluate implantation. The prototypes reached our expectations: 75% of the heads received an A score, and 25% a B score. Each implant cost approximately 7.30€ and took 5 hours for 3D-printing. The production of an economically accessible orbital implant made of biocompatible porous material was successful. Further studies will help determine if the present prototype is usable in vivo.

Protonthérapie haute énergie des tumeurs extra-oculaires, kératite neurotrophique et conséquence fonctionnelle : une série de 3 cas

High energy proton therapy (HEP) is a form of radiation therapy using protons for extraocular tumors. Its ballistic properties are theoretically advantageous, but the real impact on the surrounding ocular tissues during cerebral and ENT irradiation is poorly documented. We describe three consecutive patients with corneal damage following such irradiation. Post-proton therapy neurotrophic keratitis (NK) is defined as corneal hypo/anesthesia responsible for an alteration of corneal trophicity and graded according to the Mackie classification, in terms of a prospective ophthalmological follow-up protocol for all patients with extraocular tumors treated with HEP. Among 193 patients treated with HEP between 2018 and 2021 for extraocular tumors, three patients developed severe neurotrophic keratitis, i.e. 1.6% of treated patients. According to the Mackie classification, the three patients showed grade 3 NK less than one year after the conclusion of their HEP. These three patients underwent amniotic membrane grafting. They were placed on autologous serum eye drops. Two of the three patients had to be eviscerated. The dose to the cornea was greater than 50 Gray (Gy)_Relative biological effectiveness (RBE) in the three cases. The diagnosis and etiological origin of neurotrophic keratitis are often difficult to establish. In these cases, the imputability of radiation therapy, proton therapy in our cases, in the development of neurotrophic keratitis was plausible based on the dosimetry of the patients, all of whom had anterior tumors with a poor prognosis requiring high tumoricidal doses. Further studies to establish the impact of proton therapy on corneal sensitivity are necessary. However, this feedback and the multidisciplinary management of tumors can help to limit the risk of some complications of radiation therapy. Early diagnosis allows for appropriate management and could possibly minimize the anatomical and functional ocular complications of neurotrophic keratitis.