Ocular Surface Surgery Research Articles

A Biosynthetic Alternative to Human Amniotic Membrane for Use in Ocular Surface Surgery.

The biosynthetic Symatix membrane (SM) was developed to replace fresh human amniotic membrane (hAM) in ocular surgical applications. The purpose of this study was to test the biocompatibility of the SM with human limbus-derived epithelial cells with regard to their physical and biological properties. Different physical properties of SM were tested ex vivo by simulation on human corneas. In vitro, primary limbal epithelial cells from limbal explants were used to test biological properties such as cell migration, proliferation, metabolic activity, and limbal epithelial cell markers on the SM, hAM, and freeze-dried amniotic membrane (FDAM). The surgical handleability of the SM was equivalent to that of the hAM. Ultrastructural and histological studies demonstrated that epithelial cells on the SM had the typical tightly apposed, polygonal, corneal epithelial cell morphology. The epithelial cells were well stratified on the SM, unlike on the hAM and FDAM. Rapid wound healing occurred on the SM within 3days. Immunofluorescence studies showed positive expression of CK-19, Col-1, laminin, ZO-1, FN, and p-63 on the SM, plastic, and FDAM compared to positive expression of ZO-1, Col-1, laminin, FN, and p63 and negative expression of CK-19 in the hAM. These results indicate that the SM is a better substrate for limbal epithelial cell migration, proliferation, and tight junction formation. Altogether, the SM can provide a suitable alternative to the hAM for surgical application in sight-restoring operations. The hAM, currently widely used in ocular surface surgery, has numerous variations and limitations. The biocompatibility of corneal epithelial cells with the SM demonstrated in this study suggests that it can be a viable substitute for the hAM.

Fabrication of carboxymethyl cellulose-based thermo-sensitive hydrogels and inhibition of corneal neovascularization

Corneal neovascularization (CNV) is a common multifactorial sequela of anterior corneal segment inflammation, which could lead to visual impairment and even blindness. The main treatments available are surgical sutures and invasive drug injections, which could cause serious ocular complications. To solve this problem, a thermo-sensitive drug-loaded hydrogel with high transparency was prepared in this study, which could achieve the sustained-release of drugs without affecting normal vision. In briefly, the thermo-sensitive hydrogel (PFNOCMC) was prepared from oxidized carboxymethyl cellulose (OCMC) and aminated poloxamer 407 (PF127-NH2). The results proved the PFNOCMC hydrogels possess high transparency, suitable gel temperature and time. In the CNV model, the PFNOCMC hydrogel loading bone morphogenetic protein 4 (BMP4) showed significant inhibition of CNV, this is due to the hydrogel allowed the drug to stay longer in the target area. The animal experiments on the ocular surface were carried out, which proved the hydrogel had excellent biocompatibility, and could realize the sustained-release of loaded drugs, and had a significant inhibitory effect on the neovascularization after ocular surface surgery. In conclusion, PFNOCMC hydrogels have great potential as sustained-release drug carriers in the biomedical field and provide a new minimally invasive option for the treatment of neovascular ocular diseases.

Editorial introductions.

Editorial introductions.

Nocardia infection following ocular surface surgery

ObjectiveTo investigate the clinical characteristics and treatment outcomes of Nocardia infection after ocular surface surgery.MethodsThis is a retrospective study. Eight cases of culture-proven Nocardia infection, which developed within 1 month after ocular surface surgery were included. Demographics and clinical history of patients were investigated.ResultsThere were 8 eyes (2 left and 6 right) of 8 patients (5 males and 3 females), aged 27–65, with a median age of 52.9 years. Three cases underwent pterygium excision, three were subjected to conjunctival flap covering, and two were treated with lamellar corneal transplantation. The time interval between previous surgery and the onset of symptoms varied from 7 to 28 days (mean = 20.5 ± 7.13 days). All the cases presented grey-white infiltrates at the surgical incision site while appearing with six corneal ulcers and two conjunctival ulcers. Filaments of Nocardia were founded by confocal microscopy in two of the five cases. All responded poorly to medical therapy. Seven of the eight cases were treated with reoperation. Nocardia infection recurred in three cases after reoperation, and one was eviscerated.ConclusionsSurgical trauma is a risk factor for ocular Nocardia infection. Nocardia infection should be suspected when secondary infection occurs in a surgical incision with an atypical clinical presentation. The use of corticosteroids may influence the efficacy of drugs. Complete removal of lesions may lower the recurrence of Nocardia infection with poor drug treatment effects.

Preparing the ocular surface for glaucoma filtration surgery: an unmet clinical need

The mutual relationship among medical therapy, ocular surface (OS) and filtration surgery (FS) represents one of the most crucial issues in glaucoma management. As the long-term use of intraocular pressure-lowering medications significantly affect the OS health, patients with an uncontrolled disease frequently undergo glaucoma surgery in less-than-ideal conditions. As we known, OS changes strongly affect the post-operative bleb filtration capability. Therefore, improving the OS conditions before proceeding with FS is needed. Currently, given the rapid diffusion of new surgical procedures, this need is even more perceived. Nevertheless, despite surgeons retain the OS preparation of primary importance, and recognize the OS disease (OSD) as the only modifiable risk factor for filtration failure, there is no agreement on which strategies should be preferred to prepare patients. This is largely due to the lack of validated guidelines, which forces clinicians to adopt personal approaches based on evidence derived from low-quality studies. In this review, we provided an overview of risk factors involved in the FS failure, with particular attention to those depending on OS changes, and how OSD negatively affects the aqueous humor resorption after surgery. Moreover, we reported the most exploited measures to mitigate the OSD before surgery, the possible reasons underlying the absence of shared approaches, and the upcoming area of intervention to preserve the OS health during glaucoma management. Finally, based on the current evidence, we proposed a pre-operative outline reporting the main risk factors that should be considered before surgery, and the therapeutical options available to improve the OS.

Waves of COVID-19 Pandemic: Effect on Ocular Surface Services at a Tertiary Eye Center in India

ObjectiveTo describe the impact of lockdown and unlock phases of the coronavirus disease 2019 (COVID-19) pandemic on the ocular surface services at a tertiary eye care center in India.MethodsThis cross-sectional hospital-based study included 18,127 patients presenting between March 25, 2017, and July 31, 2021. A comparative analysis of the data was performed on the patients diagnosed with ocular surface disorders (allergic eye disease, cicatrizing conjunctivitis, dry eye, limbal stem cell deficiency, and ocular surface burns) and ocular surface surgeries (amniotic membrane grafting, keratoprosthesis, mucous membrane grafting, and simple limbal epithelial transplantation) presenting during the lockdown and unlock phases and the previous three years before COVID-19.ResultsThe outpatient numbers dropped to 18.6% (172/954) and surgeries performed decreased to 2.8% (13/461) of pre-COVID-19 volumes during the lockdown phase. This was mainly because of a 74% reduction in the proportion of patients requiring inter-state travel to this tertiary care referral center. There was a gradual recovery of the outpatient numbers to 70.8% (565/798) and surgeries performed to 85.8% (109/127) of pre-COVID-19 volumes by February-March 2021. This gradual incremental trend was seen across all diagnoses and surgeries except for ocular burns, which showed an initial spike in the month of May followed by another sharp increase by the month of September that coincided with the gradual ease of lockdown regulations. The proportion of patients requiring inter-state travel showed an incomplete recovery to 77.2% of pre-COVID-19 distribution by March 2021.ConclusionThe first year of the COVID-19 pandemic saw a drastic reduction in the outpatient numbers and surgical volume in the lockdown phase, which gradually recovered during the unlock period. However, the impact of the second wave was significant and is showing a gradual recovery in patients accessing eye care services.

Editorial introductions.

Editorial introductions.

Nano-Scale Modifications of Amniotic Membrane Induced by UV and Antibiotic Treatment: Histological, AFM and FTIR Spectroscopy Evidence.

The efficiency of amniotic membrane (AM) transplantation in different types of ocular surface disorders is due to its outstanding properties such as antifibrotic, antibacterial, anti-inflammatory and antiangiogenic, working as a versatile scaffold to promote corneal tissue epithelialization. A proper preparation, preservation and clinical application are crucial for the best outcomes in the treatment of different severe ocular disorders, taking into account its fragility. In this context, by combining high-sensitivity tools such as atomic force microscopy (AFM) and Fourier transform infrared (FTIR) spectroscopy with histological and immunohistochemical examination, we aimed to investigate the ultrastructural modifications of the amniotic membrane (AM) upon UV exposure and/or antibiotic treatment, with relevance for clinical applications in ocular surface surgery. From the morphological point of view, we noticed a loss of cuboidal cells in the basal membrane, accompanied by the splitting of collagen fibers upon UV and/or gentamicin treatment, while structural alteration of proteins was evidenced by the FTIR quantitative analysis of the secondary structure. A decrease in α-helix and β-sheet content, accompanied by increased content in less ordered structures (turns, random and side chains), was noticed after all the treatments. At the nano-scale, AFM details showed modifications of collagen fibrils in terms of their thickness and network compaction upon gentamicin and/or UV treatment. The enzymatic digestion assay demonstrated that UV exposure significantly reduces the degradation rate of the AM, while gentamicin treatment promotes an accelerated enzymatic digestion upon UV exposure. In order to highlight the clinical impact of the research, a clinical case is presented showing the relevance of amniotic membrane transplantation in pterygium surgery.

Ocular Features in a Large Cohort of Indians With Xeroderma Pigmentosum.

Xeroderma pigmentosum (XP) is an extreme hypersensitivity to sunlight causing skin freckling and pigmentary changes because of defective DNA repair mechanisms. The purpose of this article is to evaluate the spectrum of ocular and systemic features in XP at a tertiary eye care center in India over 32 years. Data from 418 eyes of 209 patients diagnosed with XP from 1987 to 2018 were reviewed retrospectively for demographics, complaints, ocular features, systemic associations, and their management. Median age at diagnosis was 2 years (interquartile range, 0.5-5 years). A total of 124 patients (59.3%) were men. There was parental consanguinity in 74.4% cases. Common ocular complaints were photophobia (47.1%), ocular discomfort (45%), defective vision (36.6%), redness (13.4%), tissue growth (12%), white spot (11.2%), and pain (10.5%). At presentation, 43.5% had corneal scars (45.5% were located inferiorly and 70.9% covered visual axis). Corneal vascularization and limbal stem cell deficiency were noted in 37.4%. A total of 56% of patients had at least 1 tumor, and 6.7% had neurological abnormalities. At least 1 ocular surgery was performed in 37.8% of patients. Ophthalmic surgical interventions included tumor excision (23%), keratoplasty (13.4%), and nontumor ocular surface surgery (3.4%). XP is a disorder that has high ocular morbidity in Indian patients. The recognition of common signs and symptoms and relative frequency of various ocular complications with time trends will help in managing and reducing the sequelae of this otherwise untreatable and progressive disease.

Changes in tear film osmolarity after 25G+ PPV

BackgroundThe aim of our study was to assess changes of tear film osmolarity after micro-incision 25G+ pars plana vitrectomy (PPV) in a prospective study.MethodsThe group consisted of 21 patients (17 women, 4 men) with an average age of 70,52 years [48; 85]. All patients underwent 25G + PPV surgery due to a disorder of the vitreomacular interface (macular hole or epimacular membrane). Only patients who did not use artificial tears before the surgery and who had not been diagnosed with dry eye syndrome at ours or another institution were included in the study. Except cataract surgery, all ocular surface diseases, intraocular diseases, trauma or surgery were exclusion criterias.Tear film osmolarity was measured in both eyes in every patient before surgery, 10 days after surgery and 30 days after surgery. A paired test was used for statistical evaluation.ResultsNo statistically significant change in osmolarity was found in the operated eyes (p > 0.05). No statistically significant changes in time (p > 0.05) were found when both eyes were compared. There were no postoperative complications or failure to observe the study protocol.ConclusionMicro-incision 25G + PPV does not affect the osmolarity of the tear film.

Sutureless and Glue-free Conjunctival Autograft in Pterygium Surgery: A Case Series

Foreign materials used in ocular surface surgery may lead to local complications such as discomfort, scarring, or infection. Plasma-derived products such as fibrin glue may produce possible hypersensitivity reactions whereas the risk of viral transmission remains. We describe a simple method of achieving conjunctival autograft adherence during pterygium surgery avoiding potential complications associated with the use of fibrin glue or sutures. Pterygium excision with limbal conjunctival autografting without using glue or sutures was performed in all the patients followed by bandaging for 24 hours. The patients were followed up post operatively on 2nd day, 1 week, 1 month, 3 month and 6 months. They were examined for haemorrhage, wound gape, graft shrinkage, chemosis, graft dehiscence, recurrence or any other complications. Total 100 cases were included in this case series. Patient age in ranged from 23 to 78 years (mean 50. 08 ± 12.76 years). Surgical Time was (in Minutes) from 20-28; mean & SD 23.76 ± 1.89. Total graft dehiscence occurred in 1 eye (1%), graft retraction in 12 eyes (12%) and recurrence was seen in 1 eye (1%). At 3 month postoperatively, the gain in uncorrected visual acuity ranged from 2-3 line in Snellen chart in 13 eyes. No other complication was noted. This simple technique for pterygium surgery may prevent potential adverse reactions encountered with the use of foreign materials and in this case series provided safe and comparable results to current methods.
 TAJ 2019; 32(2): 56-61

The Use of Bandage Contact Lens for Epithelial Healing in Corneal Epithelial Defect

Context:Corneal epithelial defect cause pain that leads to significant subjective complain, severe morbidity, and medical leave. Management of uncomplicated corneal epithelial defect using bandage contact lens (BCL) has many advantages compare to the pressure patching (traditional treatment). The use of BCL as an alternative therapy in uncomplicated epithelial defect is not yet declare as a standard protocol of treatment. Aims: To evaluate the efficacy of bandage contact lens use in patients with corneal epithelial defect compared to pressure patching in term of level of comfort, visual acquity, and wound healing period. Methods and Material: The literature search was conducted from online database. All relevant studies were reviewed based on Level of Evidence developed by Oxford Centre for Evidence-based Medicine Levels of Evidence 2011. The articles were divided into baseline characteristics and outcomes table. Details regarding the author, year of publication, level of evidence, number of samples, age, gender, follow up duration were recorded. Results: Six out of seven studies concluded that BCL is the better treatment for corneal abrasion due to trauma or related to ocular surface surgery. Four systematic reviews did not recommend pressure patching as corneal epithelial defect treatment. Conclusions: BCL was found to be superior in treating corneal abrasion compared to pressure patching. The BCL group showed significantly faster healing time, pain level reduction, and epithelial defect size reduction compare to the pressure patching group.

A Study on Sutureless and Glue-free Conjunctival Autograft in Pterygium Surgery in A Tertiary Medical College Hospital

Background: Foreign material used in ocular surface surgery may lead to local complications such as discomfort, scarring, or infection. Plasma-derived products such as fibrin glue may produce hypersensivity reactions whereas the risk of viral transmission remains. We describe a simple method of achieving conjunctival autograft adherence during pterygium surgery avoiding potential complications associated with the use of fibrin glue or sutures.
 Materials & Methods: This study was conducted at Jahurul Islam Medical college Hospital, Bajitpur, Kishoregonj from August 2016 to April 2018. Fifty cases with unilateral primary pterygium were selected for the study. The operation was done under local anaesthesia. After pterygium excision and fashioning of the autologus conjunctival graft, the recipient bed is allowed to achieve natural haemostasis and relative dessication before graft placement. Excessive haemorrhage in the graft bed is temponaded. Graft adherence and positioning is examined after surgery.
 Results: A total of 50 eyes of 50 patients mean age at the time of surgery was 40.5±10.3 years ranged from 17 to 70 years, with a female to male ratio was 1:1.94, underwent sutureless glue-free autologus conjuntival graft after pterygium excision. Mean graft area was 24(1.5) mm2. The patients were followed up for 4 months. Cosmesis was excellent in all cases and there were no intra- or post-operative complications requiring further treatment.
 Conclusion: This simple technique for pterygium surgery may prevent potential adverse reactions encountered with the use of foreign materials and this small series provided safe and comparable results to current methods.
 Anwer Khan Modern Medical College Journal Vol. 10, No. 1: Jan 2019, P 28-31

<p>Salzmann nodular degeneration: prevalence, impact, and management strategies</p>

PurposeThis review will summarize the clinical and histological presentation of Salzmann nodular degeneration (SND), its prevalence and risk factors, potential underlying mechanisms, diagnostic tools, management options, and impact on cataract surgery and co-morbid ocular surface diseases.MethodPubMed review of 44 articles published between 1976 and 2018.ResultsSND is a corneal disease characterized by whitish gray or bluish nodules on the peripheral or central cornea. The clinical presentation of SND is variable and the nodules can be asymptomatic or cause foreign body sensation and/or blurred vision. Histologically, SND appears as subepithelial nodules with thin overlying epithelium, disrupted or absent Bowman’s layer, and activated fibroblasts within the nodule. SND pathogenesis is not fully understood but is thought to involve poor epithelial protection and disruption of the epithelial–stromal interface, allowing for penetration of epithelially derived growth factors into the stroma and subsequent activation of stromal fibroblasts, eventually leading to sub-epithelial deposition of disorganized extracellular membrane components. SND most commonly occurs in Caucasian females in a bimodal distribution, occurring in the fifth or eighth and ninth decades of life. Risk factors for SND include ocular surface diseases and surgery. Surgical intervention is recommended in individuals with symptomatic nodules – primarily superficial keratectomy performed with or without intraoperative mitomycin C, photokeratectomy, and/or amniotic membrane transplantation. These procedures have been successful in removing the lesion and reducing corneal irregularity, but have variable recurrence rates (0–31%).ConclusionThe pathogenesis of SND is complex and multifactorial. Advances in diagnostic and treatment modalities have allowed for earlier and more accurate diagnosis and effective treatment of SND.

Emerging strategies for the treatment of Meibomian gland dysfunction

Meibomian gland dysfunction (MGD), as a chronic,diffuse Meibomian gland disease,is one of the most common ophthalmological clinical diseases. Symptoms can be mild,such as ocular discomfort, but severe cases resulting in ocular surface damage could affect patients' visual function. Moreover,with the absence of a thorough examination of eyelid status and Meibomian gland prior to ocular surface surgery, it could cause severe postoperative complications. As a usual but easily overlooked disease, MGD and its associated ocular surface diseases have drawn greater attention,on the other hand,some emerging therapies,in addition to the clinically recognized treatments, provided doctors with more effective treatments at their disposal,and plenty of research achievements have been published. This article emphasizes on new physical approaches in the treatments of MGD and its associated ocular surface diseases. (Chin J Ophthalmol, 2019,55:465-468).

Novel biomaterials for ocular surface surgery

Novel biomaterials for ocular surface surgery

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Editorial introductions

Evaluation of an Improved Chitosan Scaffold Cross-Linked With Polyvinyl Alcohol and Amine Coupling Through 1-Ethyl-3-(3-Dimethyl Aminopropyl)-Carbodiimide (EDC) and 2 N-Hydroxysuccinimide (NHS) for Corneal Applications.

BACKGROUND:Corneal blindness resulting from various medical conditions affects millions worldwide. The rapid developing tissue engineering field offers design of a scaffold with mechanical properties and transparency similar to that of the natural cornea.AIM:The present study aimed at to prepare and investigate the properties of PVA/chitosan blended scaffold by further cross-linking with 1-Ethyl-3-(3-dimethyl aminopropyl)-carbodiimide (EDC) and 2 N-Hydroxysuccinimide (NHS) as potential in vitro carrier for human limbal stem cells delivery.MATERIAL AND METHODS:Acetic acid dissolved chitosan was added to PVA solution, uniformly mixed with a homogenizer until the mixture was in a colloidal state, followed by H2SO4 and formaldehyde added and the sample was allowed to cool, subsequently it was poured into a tube and heated in an oven at 60°C for 50 minutes. Finally, samples were soaked in a cross-linking bath with EDC, NHS and NaOH in H2O/EtOH for 24 h consecutively stirred to cross-link the polymeric chains, reduce degradation. After soaking in the bath, the samples were carefully washed with 2% glycine aqueous solution several times to remove the remaining amount of cross-linkers, followed by washed with water to remove residual agents. Later the cross-linked scaffold subjected for various characterization and biological experiments.RESULTS:After viscosity measurement, the scaffold was observed by Fourier transform infrared (FT-IR). The water absorbency of PVA/Chitosan was increased 361% by swelling. Compression testing demonstrated that by increasing the amount of chitosan, the strength of the scaffold could be increased to 16×10−1 MPa. Our degradation results revealed by mass loss using equation shows that scaffold degraded gradually imply slow degradation. In vitro tests showed good cell proliferation and growth in the scaffold. Our assay results confirmed that the membrane could increase the cells adhesion and growth on the substrate.CONCLUSION:Hence, we strongly believe the use of this improved PVA/chitosan scaffold has potential to cut down the disadvantages of the human amniotic membrane (HAM) for corneal epithelium in ocular surface surgery and greater mechanical strength in future after successful experimentation with clinical trials.

Plasma rich in growth factors membrane as coadjuvant treatment in the surgery of ocular surface disorders.

To evaluate the safety and efficacy of the surgical use of plasma rich in growth factors fibrin membrane (mPRGF) in different ocular surface pathologies.Fifteen patients with different corneal and conjunctival diseases were included in the study. Patients were grouped according to the use of mPRGF as graft (corneal and/or conjunctival) or dressing; they were also grouped according to the surgical subgroup of intervention (persistent corneal ulcer [PCU], keratoplasty, superficial keratectomy, corneal perforation, and pterygium). Best corrected visual acuity, intraocular pressure (IOP), inflammation control time (ICT), mPRGF AT (PRGF membrane absorption time), and the healing time of the epithelial defect (HTED) were evaluated throughout the clinical follow-up time. Safety assessment was also performed reporting all adverse events.mPRGF showed a total closure of the defect in 13 of 15 patients (86.7%) and a partial closure in 2 patients (13.3%). The mean follow-up time was 11.1 ± 4.2 (4.8–22.8) months, the mean ICT was 2.5 ± 1.1 (1.0–4.0) months, the mean mPRGF AT was 12.4 ± 2.0 (10.0–16.0) days, and for the global HTED the mean was 2.9 ± 1.2 (1–4.8) months. Results showed an improvement in BCVA in all patients, with an overall improvement of 2.9 in Vision Lines. The BCVA significantly improved (P < .05) in the groups of corneal graft and dressing. In the PCU subgroup (6 patients), the healing time of epithelial defect was significantly reduced (P < .05) in patients treated only with the mPRGF in comparison to those which mPRGF therapy was associated to the amniotic membrane. The IOP remained stable (P > .05) throughout the clinical follow-up time. No adverse events were reported after mPRGF use.The mPRGF is effective and safe as coadjuvant treatment in surgeries related with ocular surface disorders, being an alternative to the use of amniotic membrane. The mPRGF accelerates tissue regeneration after ocular surface surgery thus minimizing inflammation and fibrosis.

Ocular Surface and External Filtration Surgery: Mutual Relationships.

There is a large body of evidence from clinical and experimental studies indicating that the long-term use of topical drugs may induce ocular surface changes, causing ocular discomfort, dry eye, conjunctival inflammation, subconjunctival fibrosis, corneal surface impairment, and, as a consequence of chronic ocular surface changes, the potential risk of failure for further glaucoma surgery. Subclinical inflammation has also been widely described in patients receiving antiglaucoma treatments for long periods of time, with inflammatory cell infiltration and fibroblast activation in the conjunctiva and subconjunctival space. Preservatives, especially benzalkonium chloride, which has consistently demonstrated its toxic effects in laboratory, experimental, and clinical studies, could induce or enhance such inflammatory changes, and has been recently confirmed as a direct risk factor of surgical failure. As a quaternary ammonium, this compound causes tear film instability, loss of goblet cells, conjunctival squamous metaplasia and apoptosis, disruption of the corneal epithelium barrier, corneal nerve impairment, chronic inflammation and potential damage to deeper ocular tissues. Drug-induced adverse effects are therefore far from restricted to only allergic reactions, but they are often very difficult to identify because they mostly occur in a delayed or poorly specific manner, and result from complex and multifactorial interactions between the drugs and the ocular surface. Postoperatively, the ocular surface also plays an important role, as the conjunctiva interacts with aqueous humor and subconjunctival fibrosis may block aqueous outflow and cause surgical failure. As preoperative inflammation underlies postoperative fibrosis and therefore surgical outcome, a better knowledge of ocular surface changes with appropriate evaluation and management should thus become a new paradigm in glaucoma care over the long term.