DMEK surgical training: An instructional guide on various wet-lab methods.

Descemet membrane endothelial keratoplasty (DMEK) is a partial-thickness corneal transplantation procedure that involves selective transplantation of the Descemet membrane and endothelium. DMEK offers significant advantages over other keratoplasty techniques, such as faster visual rehabilitation, better final visual acuity due to minimal optical interface effects, lower risk of allograft rejection, and less long-term dependence on topical steroids. Despite all its advantages, DMEK has been found to be more challenging than other corneal transplantation techniques, and its steep learning curve appears to be an obstacle to its widespread use and adoption by corneal surgeons worldwide. DMEK surgical training laboratories (wet labs) provide a window of opportunity for surgeons to learn, prepare, manipulate, and deliver these grafts in a risk-free environment. Wet labs are a significant learning tool, especially for those institutions that have limited tissue availability in their local centers. We provide a step-by-step guide for preparing DMEK grafts using different techniques on human and nonhuman models with instructional videos. This article should eventually help the trainees and the educators understand the requirements for performing DMEK and conducting a DMEK wet lab and develop their skills and interests from a wide variety of available techniques.

Ocular-Surface Regeneration Therapies for Eye Disorders: The State of the Art.

The ocular surface is a complex structure that includes cornea, conjunctiva, limbus, and tear film, and is critical for maintaining visual function. When the ocular-surface integrity is altered by a disease, conventional therapies usually rely on topical drops or tissue replacement with more invasive procedures, such as corneal transplants. However, in the last years, regeneration therapies have emerged as a promising approach to repair the damaged ocular surface by stimulating cell proliferation and restoring the eye homeostasis and function. This article reviews the different strategies employed in ocular-surface regeneration, including cell-based therapies, growth-factor-based therapies, and tissue-engineering approaches. Dry eye and neurotrophic keratopathy diseases can be treated with nerve-growth factors to stimulate the limbal stem-cell proliferation and the corneal nerve regeneration, whereas conjunctival autograft or amniotic membrane are used in subjects with corneal limbus dysfunction, such as limbal stem-cell deficiency or pterygium. Further, new therapies are available for patients with corneal endothelium diseases to promote the expansion and migration of cells without the need of corneal keratoplasty. Finally, gene therapy is a promising new frontier of regeneration medicine that can modify the gene expression and, potentially, restore the corneal transparency by reducing fibrosis and neovascularization, as well as by stimulating stem-cell proliferation and tissue regeneration.

Thyroglobulin Value Predict Iodine-123 Imaging Result in Differentiated Thyroid Cancer Patients.

Background: In differentiated thyroid cancer (DTC) patients, the response to initial treatments is evaluated 6-12 months after radioiodine therapy (RIT) according to the 2015 American Thyroid Association (2015 ATA) criteria. In selected patients, diagnostic 131-radioiodine whole-body scintigraphy (Dx-WBS) is recommended. We evaluated the diagnostic performance of 123I-Dx-WBS-SPECT/CT imaging in detecting incomplete structural responses in the early follow-up of DTC patients and, additionally, derived optimized basal-Tg value as a yardstick for scintigraphic imaging. Methods: We reviewed the records of 124 low or intermediate-risk DTC patients with negative anti-thyroglobulin antibody. All patients had undergone (near)-total-thyroidectomy followed by RIT. The response to initial treatments was evaluated 6-12 months after RIT. Results: According to the 2015 ATA criteria, 87, 19 and 18 DTC patients were classified to have excellent response (ER), indeterminate/incomplete biochemical response (BIndR/BIR) or structural incomplete response (SIR), respectively. Among patients with less than ER, 18 had a positive 123I-Dx-WBS-SPECT/CT. Metastatic disease at 123I-Dx-WBS-SPECT/CT mainly involved lymph nodes within the central compartment, and corresponding neck ultrasound examinations were negative. The ROC curve analysis was performed to define the best basal-Tg cut-off (i.e., 0.39 ng/mL; AUC = 0.852) able to discriminate patients with and without positive 123I-Dx-WBS-SPECT/CT, respectively. The overall sensitivity, specificity, accuracy, PPV and NPV were 77.8%, 89.6%, 87.9%, 56.0% and 95.9%, respectively. Basal-Tg cut-off was an independent risk factor for having a positive 123I-Dx-WBS-SPECT/CT. Conclusion:123I-Dx-WBS-SPECT/CT identified lymph node metastases in 14/37 patients with less than ER and a negative neck ultrasound, thus modifying the management of such patients. The diagnostic performance of 123I-Dx-WBS-SPECT/CT significantly increased in patients with basal-Tg values ≥ 0.39 ng/mL.

Managing Post-Keratoplasty Astigmatism: High-Tech vs. Low-Tech Imaging Techniques for Guiding Suture Manipulation.

Astigmatism is a visually significant condition that can develop after keratoplasty. The management of post-keratoplasty astigmatism can be performed both when transplant sutures are in place and when they have been removed. Fundamental for astigmatism management is its identification and characterization in terms of type, amount, and direction. Commonly, post-keratoplasty astigmatism is evaluated through corneal tomography or topo-aberrometry; however, many other techniques can be used in case these instruments are not readily available. Here, we describe several low-tech and high-tech techniques used for post-keratoplasty astigmatism detection in order to quickly understand if it contributes to low vision quality and to determine its characteristics. The management of post-keratoplasty astigmatism through suture manipulation is also described.

Incidence and management of early postoperative complications in lamellar corneal transplantation.

PURPOSE: To provide a comprehensive review of the incidence, risk factors, and management of early complications after deep anterior lamellar keratoplasty (DALK), Descemet stripping automated keratoplasty (DSAEK), and Descemet membrane endothelial keratoplasty (DMEK). METHODS: A literature review of complications, that can occur from the time of the transplant up to 1 month after the transplant procedure, was conducted. Case reports and case series were included in the review. RESULTS: Complications in the earliest postoperative days following anterior and posterior lamellar keratoplasty have shown to affect graft survival. These complications include, but are not limited to, double anterior chamber, sclerokeratitis endothelial graft detachment, acute glaucoma, fluid misdirection syndrome, donor-transmitted and recurrent infection, and Uretts-Zavalia syndrome. CONCLUSION: It is essential for surgeons and clinicians to not only be aware of these complications but also know how to manage them to minimize their impact on long-term transplant survival and visual outcomes.

Preliminary Findings of the Role of FAPi in Prostate Cancer Theranostics.

Prostate cancer (PCa) is the most frequently diagnosed cancer worldwide and the second most common cause of cancer-related deaths among men. Progress in molecular imaging has magnified its clinical management; however, an unmet clinical need involves the identification of new imaging biomarkers that complement the gold standard of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in cases of clinically significant PCa that do not express PSMA. Fibroblast activation protein (FAP) is a type II transmembrane serine overexpressed in many solid cancers that can be imaged through quinoline-based PET tracers derived from an FAP inhibitor (FAPi). Preliminary results of FAPi application in PCa (in PSMA-negative lesions, and in comparison with fluorodeoxyglucose-FDG) are now available in the literature. FAP-targeting ligands for PCa are not limited to detection, but could also include therapeutic applications. In this preliminary review, we provide an overview of the clinical applications of FAPi ligands in PCa, summarising the main results and highlighting contemporary strengths and limitations.

Selective laser capsulotomy complications: Management and prevention.

PURPOSE: To report how to manage and prevent the incomplete laser cut and following uncut tags of anterior capsular lens, performed using the selective laser capsulotomy. METHODS: We describe three possible approaches: peeling the anterior capsulotomy disc with forceps, breaking the tags using the cystotomy needle tip, or cutting them using a 23-G vitrectomy scissors. RESULTS: Using the 23-G vitrectomy scissors resulted in no complication. Peeling the anterior capsulotomy using the forceps instead caused zonular stress with subsequent risks of zonular dialysis, whereas using the cystotomy needle tip resulted in irregular capsulotomy rim and weakness all along the capsulotomy edge where micro tears caused a tear during the rest of cataract surgery. CONCLUSION: Incomplete laser cut and subsequent discontinuous capsulotomy results in the presence of multiple tags which create strong adherence between the central capsulotomy disc and the peripheral capsule. Key steps of the procedure to prevent an incomplete laser cut, which are the anterior lens capsule staining and laser beam focusing, and how to correctly manage them, which may shorten the learning curve and enhance the outcomes.

Descemet membrane endothelial keratoplasty graft detachments in superior versus temporal approach.

PURPOSE: To evaluate the difference in Descemet Membrane Endothelial Keratoplasty (DMEK) graft detachment rate comparing superior versus temporal main incision approach. METHODS: Retrospective comparative study on patients who underwent DMEK surgery for Fuchs endothelial dystrophy or bullous keratopathy with main wound incision performed at either 90° in the superior approach, or at 180°/0° in the temporal approach. All main incisions were secured with a single 10-0 nylon suture at the end of surgery. Data collected were donor age and gender, endothelial cell counts, graft diameter, recipient age and gender, indication for transplant, surgeon grade, re-bubbling rate, air fill in the anterior chamber (AC) at day one and intra- and early postoperative complications. RESULTS: 187 eyes were included in the study. 99 eyes had DMEK surgery with superior approach, while 88 eyes had temporal approach. The two groups had no differences in donor age and sex, endothelial cell counts, graft diameter, recipient age and sex, indication for transplant, surgeon grade, and air fill in the anterior chamber at day one. Re-bubbling rate was 38.4% for surgeries performed with superior access and 29.5% for those with temporal access(p = 0.186). After exclusion of patients with intraoperative and/or postoperative complication, the difference in re-bubbling rate was higher, although non-significant (37.5% and 25% for superior and temporal approach respectively, p = 0.098). CONCLUSION: The temporal approach in DMEK showed a trend towards a clinically significant lower rate of post-operative re-bubbling compared to the superior approach, however, no statistically significant difference was noted comparing the two approaches, which both remain feasible options in DMEK surgery.

Artificial iris implantation in congenital aniridia: A systematic review.

Congenital aniridia is a rare, panocular disorder with a main phenotypic characteristic of a partial or complete absence of the iris existing alongside other ocular morbidities such as cataract, keratopathy, optic nerve and foveal hypoplasia, and nystagmus. The iris abnormality, however, often leads to symptoms such as photophobia, glare, and decreased visual acuity, as well as cosmetic dissatisfaction. Current management options for the iris deficit include colored iris contact lenses, corneal tattooing, and tinted contact lenses. Symptoms arising from small iris defects can be resolved with surgical management using micro-tying suture techniques such as McCannel or Siepser. Currently, larger iris defects can be treated with artificial iris implants. New prosthetic options range from colored intraocular lenses to flexible custom-made silicone iris implants. With a range of therapeutic options available and given the challenges of multiple comorbidities in aniridia, we evaluate the literature relating to the use of artificial iris implants in congenital aniridia, with a focus on the different surgical implantation techniques, the clinical outcomes achieved, complications occurred, and risk of bias of the studies included.

DMEK graft: One size does not fit all.

Descemet membrane endothelial keratoplasty (DMEK) is a popular procedure for the treatment of corneal endothelial diseases mainly targeting Fuchs endothelial corneal dystrophy (FECD) and pseudophakic bullous keratopathy (PBK). Although DMEK has multiple advantages, it is challenging in terms of graft preparation and delivery. One of the crucial factors of DMEK graft preparation is determining the size of the graft. Evaluating risks and benefits of transplanting larger or smaller grafts compared with the descemetorhexis performed following a standard DMEK procedure thus becomes important. Advanced techniques like pre-loaded DMEK requires pre-selection of graft diameter without physical examination of the eye making it more challenging. Therefore, recognizing the benefits of graft size and the number of transplanted endothelial cells becomes essential. Smaller DMEK grafts have been preferred and accepted for grafting. Larger diameter grafts have advantages but can be challenging due to higher detachment rates. We thus aim to review the challenges of preparing and delivering DMEK tissues with small or large diameter based on selected descemetorhexis area, discuss the outcomes based on different graft sizes, highlight related complications and suggest which cases may benefit from adopting smaller or larger graft size.

Carlevale intraocular lens opacification after Descemet stripping automated endothelial keratoplasty.

PURPOSE: To report a case of sutureless scleral-fixated (SSF) Carlevale intraocular lens (IOL) opacification following Descemet stripping automated endothelial keratoplasty (DSAEK) surgery. METHODS: An 82-year-old man underwent combined SSF Carlevale IOL implant and DSAEK surgery for aphakic endothelial decompensation. Surgery was uneventful, while the postoperative period was complicated by multiple graft detachments requiring re-bubbling. After four re-bubbling procedures, the corneal graft attached and cleared over time. RESULTS: 29 months after combined SSF IOL implant and DSAEK surgery, the patient presented with decreased vision due to IOL opacification affecting the visual axis. CONCLUSION: Although combined SSF IOL and DSAEK surgery is an overall safe and effective procedure for aphakic endothelial decompensation, risk of IOL opacification due to anterior chamber air injection is higher when using hydrophilic IOLs and in cases requiring multiple re-bubbling, therefore, intraocular lens material should be chosen after considering the risks and benefits.

Posterior stromal ripples increase risk of Descemet's membrane endothelial keratoplasty graft detachment worsening over time.

PURPOSE: To evaluate anterior segment optical coherence tomography (AS-OCT) features of Descemet's membrane endothelial keratoplasty (DMEK) grafts associated with graft attachment worsening over time. METHODS: Retrospective case series on patients who received uncomplicated DMEK surgery and for whom subsequent AS-OCT data were available for analysis. Patients' demographics and surgical details were collected. AS-OCT was analysed for graft detachment axial extension, presence of posterior stromal ripples, quadrant involvement (location and number), degree of detachment extension, peripheral roll, presence and amount of air in the anterior chamber (AC). Features associated with re-bubbling and graft detachment worsening over time were identified. RESULTS: A total of 147 patients with a mean age of 70.8 ± 9.8 years (63% females) were included. AS-OCT was performed at 2.9 ± 2.4 days after surgery. AS-OCT factors associated with re-bubbling were posterior stromal ripples (p = 0.004) and detachment axial extension (p < 0.001). At first follow-up, of the 147 DMEK, 67 showed complete attachment and 80 partial detachment. In those cases of initially completely attached grafts, posterior stromal ripples were associated with the risk of subsequent graft detachment (p = 0.014) together with recipient age (p = 0.043), phaco-combined surgery (p = 0.018) and AS-OCT timing (p = 0.033); while, in the initially partially detached grafts, detachment worsening was associated with posterior stromal ripples (p = 0.025), detachment axial extension (p = 0.003), degrees of detachment involvement (p = 0.029), peripheral roll-in shape (p = 0.033) and presence of air in the AC (p = 0.032). Relative risk (RR) of graft detachment worsening in patients with moderate/severe posterior stromal ripples was 1.75 (95% CI = 1.09-2.81). CONCLUSION: Posterior stromal ripples and detachment axial extension >1/3 of graft surface area were the main risk factors for detachment worsening over time, and patients showing these features should be monitored closely to identify the need for re-bubbling at an early stage, thus improving surgical outcomes.

Therapeutic Hyper-CL soft contact lens in Sjögren's syndrome.

Purpose: To report increased corneal bioavailability of allogenic serum when used in combinations with Therapeutic Hyper-CL™ soft contact lens in a patient with severe Sjögren's syndrome-associated dry eye. Observations: A 57-year-old woman with a medical history of bilateral severe Sjögren's syndrome-associated dry eye and previous amniotic membrane patch for autoimmune corneal perforation in her left eye was referred for left eye recurrence of progressive melting and pending perforation. After manual corneal trephination, full thickness transplant and sutured amniotic membrane patch, a Therapeutic Hyper-CL™ soft contact lens (EyeYon Medical, Ness Tziona, Israel) was fit. The patient was commenced in the left eye with topical corticosteroid, antibiotic, and allogenic serum eye drops. In the right eye the patient had silicone hydrogel bandage contact lens and was under same treatment of the left eye for previous endothelial keratoplasty. In order to evaluate the efficacy and increased corneal availability of drugs provided by Therapeutic Hyper-CL™ compared with silicone hydrogel soft contact lens, anterior segment OCT was performed. Conclusions and importance: The anterior segment OCT showed a thicker meniscus of fluid and possibly subsequent increase of trophic factors bioavailability in left eye compared with right eye. Therefore, in case of severe and refractory dry-eye disease the combination of Therapeutic Hyper-CL™ and serum eye drops may be representing a valid therapeutic approach.

COVID-19 AdenoviralVector Vaccine and Central Retinal Vein Occlusion.

PURPOSE: The purpose of this article is to report a case of sudden onset ischemic retinal central vein occlusion after a second dose of COVID-19 adenoviral vector vaccine. CASE REPORT/OBSERVATIONS: A 54-year-old woman with systemic arterial hypertension developed ischemic central retinal vein occlusion in her right eye on day 2 after the second dose of COVID-19 adenoviral vector vaccine ChAdOx1 nCoV-19/ AZD1222, Oxford-AstraZeneca. CONCLUSION: Adenoviral vector vaccine promotes both cellular and humoral immune responses, increasing the level of inflammatory cytokines. These cytokines are the same implied in the possible pathogenesis of central retinal vein occlusion. Subsequently, we recommend informing patients at risk of possible ocular adverse events, which require urgent evaluation.

Myopia: Mechanisms and Strategies to Slow Down Its Progression.

This topical review aimed to update and clarify the behavioral, pharmacological, surgical, and optical strategies that are currently available to prevent and reduce myopia progression. Myopia is the commonest ocular abnormality; reinstated interest is associated with high and increasing prevalence, especially but not, in the Asian population and progressive nature in children. The growing global prevalence seems to be associated with both genetic and environmental factors such as spending more time indoor and using digital devices, particularly during the coronavirus disease 2019 pandemic. Various options have been assessed to prevent or reduce myopia progression in children. In this review, we assess the effects of several types of measures, including spending more time outdoor, optical interventions such as the bifocal/progressive spectacle lenses, soft bifocal/multifocal/extended depth of focus/orthokeratology contact lenses, refractive surgery, and pharmacological treatments. All these options for controlling myopia progression in children have various degrees of efficacy. Atropine, orthokeratology/peripheral defocus contact and spectacle lenses, bifocal or progressive addition spectacles, and increased outdoor activities have been associated with the highest, moderate, and lower efficacies, respectively.

Importance of Corneal Angiography in Subclinical Limbitis in a Case of Atopic Keratoconjunctivitis.

PURPOSE: The aim of this study was to report corneal angiography features in subclinical limbitis in a patient with atopic keratoconjunctivitis. METHODS: This is a case report. RESULTS: A 22-year-old woman with a medical history of atopic keratoconjunctivitis was referred for bilateral corneal neovascularization with scarring. On examination, no signs of active disease were noticed at the slit lamp. Ocular surface angiography detected active corneal limbitis, showing as limbal leakage at fluorescein angiography in the early phase and leakage after indocyanine green angiography in the late phase. The patient was treated with topical corticosteroid. At follow-up, the fluorescein angiography and indocyanine green angiography no longer showed limbal leakage, whereas the slit lamp examination was unchanged. CONCLUSIONS: Active allergic corneal limbitis may present as subclinical inflammation, with no signs of activity at the slit lamp examination. Therefore, its diagnosis can be challenging without the use of corneal angiography.

Blast Wound Dehiscence During Descemet Membrane Endothelial Keratoplasty Rebubbling in a Previous Penetrating Keratoplasty: A Case Report.

PURPOSE: The purpose of this study was to describe a rare complication of Descemet membrane endothelial keratoplasty (DMEK) rebubbling. METHODS: An 86-year-old woman with bilateral penetrating keratoplasty (PK) performed 20 years previously for Fuchs endothelial dystrophy underwent DMEK surgery for endothelial corneal decompensation in the left eye. Surgery was complicated in the postoperative period by repeated DMEK graft detachments requiring rebubbling. RESULTS: The third rebubbling procedure caused a traumatic PK wound dehiscence at the graft-host junction with full-thickness opening of approximately 180 degrees. PK wound dehiscence was resutured in the theater, DMEK lenticule was removed from the eye, and the full-thickness graft was repeated. CONCLUSIONS: DMEK graft rebubbling in patients with previous PK may lead to traumatic wound dehiscence. Avoidance of excessive increases in intraocular pressure during the rebubbling procedure should be encouraged to decrease the risk of this rare complication.

Keratoconus detection of changes using deep learning of colour-coded maps.

OBJECTIVE: To evaluate the accuracy of convolutional neural networks technique (CNN) in detecting keratoconus using colour-coded corneal maps obtained by a Scheimpflug camera. DESIGN: Multicentre retrospective study. METHODS AND ANALYSIS: We included the images of keratoconic and healthy volunteers' eyes provided by three centres: Royal Liverpool University Hospital (Liverpool, UK), Sedaghat Eye Clinic (Mashhad, Iran) and The New Zealand National Eye Center (New Zealand). Corneal tomography scans were used to train and test CNN models, which included healthy controls. Keratoconic scans were classified according to the Amsler-Krumeich classification. Keratoconic scans from Iran were used as an independent testing set. Four maps were considered for each scan: axial map, anterior and posterior elevation map, and pachymetry map. RESULTS: A CNN model detected keratoconus versus health eyes with an accuracy of 0.9785 on the testing set, considering all four maps concatenated. Considering each map independently, the accuracy was 0.9283 for axial map, 0.9642 for thickness map, 0.9642 for the front elevation map and 0.9749 for the back elevation map. The accuracy of models in recognising between healthy controls and stage 1 was 0.90, between stages 1 and 2 was 0.9032, and between stages 2 and 3 was 0.8537 using the concatenated map. CONCLUSION: CNN provides excellent detection performance for keratoconus and accurately grades different severities of disease using the colour-coded maps obtained by the Scheimpflug camera. CNN has the potential to be further developed, validated and adopted for screening and management of keratoconus.