Simultaneous Muraine Sutures and Excimer Laser-Assisted Penetrating Keratoplasty for Acute Keratoconus.

Background: Acute keratoconus (acute KC), which affects approximately 1.6-2.8% of keratoconus (KC) patients, is a pathological condition of the cornea characterized by stromal edema due to entry of aqueous humor through a tear in Descemet's membrane. Methods: We present a novel combination of surgical procedures that allows swifter visual recovery in a consecutive, retrospective case series. The new surgical procedure for acute KC consists of a combination of Muraine corneal sutures to smooth the corneal curvature and Excimer laser-assisted penetrating keratoplasty and was performed in six acute KC patients from 2019 to 2022 at the Department of Ophthalmology, University Hospital of Martin-Luther-University Halle-Wittenberg (UMH), Germany. We monitored data on preoperative status, operative details, intraoperative and postoperative complications and visual outcomes were analyzed. Results: The mean age was 41.5 ± 13.5 years (3 OD, 3 OS). Neurodermatitis was present in 3 patients (50%). All patients received significant visual benefits from the procedure. Preoperative BCVA was hand motion (logMAR 3.0) in all patients; postoperatively, BCVA improved significantly logMAR 0.03 ± 0.09 [range: 0.2-0.4; p < 0.001, FUP 20+/-10 months). Visual acuity remained stable throughout the roughly biannual follow-ups. One patient developed endothelial graft rejection after 2 years. During the last examination, all eyes had clear grafts and stable curvatures, K1 and K2 being 42.43 ± 4.17 D and 44.95 ± 4.07 D, respectively, and mean corneal astigmatism was 2.61 ± 1.74 D. The thinnest corneal thickness was 519 ± 31 µm. A graft size of 8.0 × 8.1 mm was the most beneficial. Conclusions: in patients with acute KC and hydrops, a penetrating keratoplasty with Muraine corneal sutures is successful in terms of graft clarity and visual outcome. Combining the procedures allows quicker visual recovery. Patients with a history of neurodermatitis should have preoperative and postoperative dermatologic treatment and close follow-up for possible complications.

Intraocular Epithelial Ingrowth after Traumatic and Surgical Corneal Injuries.

Intraocular epithelial ingrowth is a rare but serious complication of eye surgery or trauma. The diagnosis is challenging but can be aided by techniques such as anterior optical coherence tomography (AS-OCT). This study aimed to compare clinical and histopathological diagnostic data to evaluate the accuracy of AS-OCT. This retrospective analysis focused on patients presenting with suspected epithelial invasion between 2017 and 2022. Clinical data and histopathological findings were analyzed for diagnostic confirmation. Immunohistochemistry using the corneal-specific marker cytokeratin 3 and the conjunctival-specific marker cytokeratin 13 helped to identify the type of invading epithelial cells. Statistical analysis was used to evaluate the effectiveness of AS-OCT for diagnosis. This study included 51 patients who underwent keratoplasty or enucleation. Sixteen cases (31%) of epithelial ingrowth were histologically confirmed. The most common type was the cystic form (82%). Enucleation was required in 25% of patients, mainly due to diffuse epithelial invasion. Immunohistochemistry revealed a conjunctival origin in 82% of the infiltrated cells. AS-OCT showed a sensitivity of 78% and a specificity of 26% in detecting hyperreflective structures associated with epithelial invasion. This study highlights the diverse manifestations of epithelial ingrowth and the need for improved diagnostic techniques, with AS-OCT showing promising results but requiring further validation to avoid misdiagnosis.

Augenverätzungen.

Chemical burns of the ocular surface (CBOS) are emergencies of highest urgency. Therefore, an adequate emergency care is mandatory. Following a precise analysis of the initial damage, a staged therapeutic approach is used to prevent persistent impairment of the ocular surface. In the acute stage, the prevention of complications is targeted (symblepharon, conjunctival scarring, lacrimal stenosis, corneal ulceration, intraocular inflammation, elevated intraocular pressure, etc.). In later stages, if complications have developed, a secondary restoration of the ocular surface is focussed. Sometimes this requires several surgical interventions. Based on a review of international literature, this review highlights the pathophysiology according to different chemical agents, CBOS stages as well as main therapy strategies in early and advanced stages of CBOS. Acute treatment aims to lower inflammation, oxidative stress and tries to promote reepithelialisation. Besides conjunctival scarring, loss of goblet cells and corneal opacification a limbal stem cell insufficiency is the most harming complication. Several new techniques have been developed to recover the ocular surface with a sufficient and clear epithelial layer in order to avoid neovascularization of the cornea. The knowledge concerning the high risk potential for persistent visual impairment in CBOS patients and the ability for appropriate emergency care should be kept in every physician's mind dealing with CBOS.

Evaluation of the Possible Influence of Povidone Iodine (PVI) Solution and Polyhexanide (PHMB) on Wound Healing in Corneal Epithelial Regeneration.

This study investigates the possible toxic effects of the preoperative antiseptic substances povidone iodine (PVI) and polyhexanide (PHMB; Serasept® 2) on wound healing in ophthalmology. To assess this impact, human telomerase-immortalized corneal epithelial (hTCEpi) cells and human telomerase-immortalized conjunctival epithelial (hCjE) cells were exposed to 1% and 5% PVI or 0.04% PHMB for different periods to evaluate the cytotoxicity of these two antiseptics. Furthermore, the toxicity of these antiseptics was investigated in a human tissue-specific corneal epithelial construct and porcine eye culture model. The results reveal the high cytotoxicity of PVI and PHMB in the hTCEpi and hCjE in monolayer cell culture models, independent of the incubation time and concentration of these substances. However, after hTCEpi cell differentiation into a tissue-specific corneal epithelial construct, contact with these antiseptics for the relevant preoperative time did not alter cPARP1 or Ki67 expression. Furthermore, the wound-healing process in the porcine cornea was not significantly influenced after incubation with these antiseptics. In summary, corneal and conjunctival epithelial cell lines are very sensitive to PVI and PHMB, whereas no significant alterations were found in intact tissue-specific corneal epithelial constructs or porcine corneas. Therefore, we could not identify PVI and PHMB as reasons for postoperative eye irritation.

Transcutaneous (External) Dacryocystorhinostomy with Reconstruction of the Ductus nasolacrimalis. / Transkutane (externe) Dakryozystorhinostomie mit Rekonstruktion des Ductus nasolacrimalis.

BACKGROUND: Dacryocystorhinostomy (DCR) is regarded as the gold standard for the treatment of chronic dacryocystitis (CDC). Different modifications of the surgical procedure have been developed over the years. METHODS: Patients with CDC due to postsaccal lacrimal stenosis and under treatment with DCR have been included in this retrospective study. Two groups of different surgical procedures were analysed: firstly DCR without reconstruction of the ductus nasolacrimalis (DNL, group 1) and secondly patients with reopening the DNL (group 2). Criteria for success were absence of permanent epiphora, absence of inflammation of the lacrimal sac (functional success), and no recurrent surgery with free patency of the lacrimal duct (anatomical success). This was obtained by questionnaire after a follow-up of at least 12 months. The impact of gender, ectasia of the lacrimal sac, dacryoliths, and prior lacrimal surgeries was analysed. RESULTS: Overall, 248 surgeries were enrolled in this trial. Mean age in group 1 was 68 years (range: 22 to 92 years) and gender ratio was 3.2 to 1 (female : male). In that group, 68 operations could be followed up. In group 2, 62 operations on patients of a mean age of 63 years (range: 24 to 89 years) and a gender ratio of 2.9 to 1 (female : male) were observed. Complete success occurred in 75.0% in group 1 and 75.8% in group 2. Recurrent operations were necessary in one case of group 2 (1.6%) and 4 cases of group 1 (5.9%). Gender (group 1 p = 1; group 2 p = 0.115; between groups p = 0.511), ectasia of the lacrimal sac (group 1 p = 0.877; group 2 p = 0.674; between groups p = 0.878), dacryolith (group 1 p = 1; group 2 p = 0.465; between groups p = 1), and prior lacrimal surgery (group 1 p = 0.092; group 2 p = 0.051; between groups p = 0.520) did not influence the success rates in each group or between groups. Significantly more dacryoliths were found during operations of group 2 (p = 0.010). CONCLUSION: Reconstruction of the DNL during DCR is a possible and easy modification, with a slightly better success rate in curing CDC. Intraoperatively, dacryoliths might not be apparent remain in the deeper parts of the lacrimal ducts. Therefore, these segments should be inspected during surgery.

Pressure-Lowering Effect of Interventional Fistula Occlusion in Secondary Glaucoma due to Orbital Draining Intracerebral Fistulae. / Drucksenkender Effekt der interventionellen Fistelokklusion bei Sekundärglaukom infolge orbital drainierender intrazerebraler Fisteln.

BACKGROUND: Carotid cavernous sinus fistulas (CSCF) are pathological connections of the internal and/or external carotid artery (and/or its branches) to the cavernous sinus. Ophthalmological symptoms and problems occur particularly when drainage is via the superior ophthalmic vein. MATERIAL AND METHODS: Seven eyes of six patients with a high-grade suspicion of CSCF were included in this retrospective monocentric study. Digital subtraction angiography (DSA) was performed in the included patients, where an interventional fistula closure was performed in the case of CSCF. Four of the six patients received a pre- and post-interventional day-night intraocular pressure profile. Furthermore, medical history, symptoms, visual acuity, slit lamp microscopic findings, and DSA findings were evaluated. RESULTS: The most common symptoms reported by patients were red eyes, diplopia, and exophthalmos. When the intraocular pressure (IOP) was measured, 83.33% of the patients showed increased values. The mean IOP in the day-night intraocular pressure profile in the affected eye before intervention was 23.5 (± 2.7) mmHg compared to 14.1 (± 2.3) mmHg in the healthy eye. A significant difference could thus be demonstrated in side comparison (p = 0.0047). The post-interventional measurement showed a mean IOP of 15.3 (± 1.0) mmHg in the affected eye and thus a significant difference to the pre-interventional measurement in the affected eye (p = 0.0018). Four of the six patients with CSCF were taking antiglaucomatous eye drops before the intervention, and two patients after the intervention. The number of antiglaucoma drugs used could also be reduced. CONCLUSION: Interventional fistula closure is an effective method for treating the secondary increase of IOP in CSCF. Successful closure of the fistula showed a significant reduction in IOP, which was not possible with the sole administration of antiglaucoma drugs. Radius-Maumenee syndrome should be considered as a differential diagnosis.

[Concrements of the lacrimal apparatus]. / Konkremente des Tränenapparates.

Concrements of the lacrimal apparatus, known as dacryoliths, can occur at different localizations and can cause a variety of symptoms. A common clinical sign is chronic inflammation, possibly exhibiting acute exacerbation. Based on a literature review and descriptive clinical cases with histopathological correlations, this contribution summarises the most important information concerning epidemiology, aetiopathogenesis, composition, histology, and therapy of lacrimal concrements. Furthermore, factors known to affect lacrimal lithogenesis are addressed. Concrements of the lacrimal gland cause a swelling at the lateral canthus. With only mild pain, this manifests as circumscribed conjunctival hyperaemia. Histologically, the gland tissue is characterised by acute-erosive to chronic inflammation. The concrements consist of amorphic material. Inflammatory infiltration is dominated by neutrophil granulocytes. Canalicular concrements are highly correlated with chronic canaliculitis. Besides epiphora, patients present with purulent discharge at the affected canaliculus. Actinomyces are frequently found inside these deposits and form drusen-like formations. The surrounding tissue reacts with plasma-cellular and granulocytic inflammation. Dacryoliths (concrements of the lacrimal sac) are associated with dacryocystitis, whereby acute and chronic types are common. Stones can be found in up to 18% of patients undergoing dacryocystorhinostomy or dacryoendoscopy. Preoperative diagnostic testing is challenging, as many lacrimal sac stones cannot be reliably visualised by diagnostic procedures. Recurring episodes of epiphora, mucopurulent discharge, and dacryocystitis are common indicators of dacryoliths. Lacrimal syringing is often possible and shows that total blockage is not present. Histology of the lacrimal mucosa reveals lymphocytic infiltration and submucosal fibrosis. The immediate vicinity of the dacryoliths shows acute inflammation. Therapy consists of stone extraction and improving lacrimal drainage, as the latter is recognised as the main risk factor for dacryolith formation.

Repetitive Bleomycin-Based Electrochemotherapy Improves Antitumor Effectiveness in 3D Tumor Models of Conjunctival Melanoma.

BACKGROUND: Conjunctival melanoma (CM) is associated with a high rate of local recurrence and poor survival rate. Novel therapeutic options are needed to reduce recurrence rate. The objective of the study was to demonstrate the improved effectiveness of electrochemotherapy (ECT) on CM using repetitive application. METHODS: Tumor spheroids of three CM cell lines (CRMM1, CRMM2, CM2005.1) were treated repetitively with ECT using the chemotherapeutic agent bleomycin on days 3, 5, and 7 of culture. Application of bleomycin alone and electroporation alone served as controls. The cytotoxic effect was analyzed on day 10 compared to untreated control using an independent t-test. The spheroid outgrowth rate was measured. RESULT: CM tumor spheroid size (median value: 78%, SD: 32%) and viability (median value: 11%, SD: 11%) were dramatically reduced after repetitive ECT treatment (p-value < 0.001). Decreased proliferation capacity (down to 8%) and an increase of apoptotic cells were observed. In most repetitive ECT-treated spheroids, no viable or proliferating cells were detected. Only 33-40% of repetitive ECT-treated spheroids exhibited single outgrowing cells with a delay of time up to 38 days. CONCLUSION: Repetitive ECT application effectively induces cytotoxic effects in CM spheroids by inducing apoptosis, inhibiting proliferation and decreasing the percentage of surviving tumor cells. Thus, repetitive ECT results in improved antitumor effectiveness in CM and could be an alternative therapy option.

Allogeneic Limbal Transplants Integrate into the Corneal Surface and Lead to an Improved Visual Acuity.

Limbal stem cell deficiency (LSCD) severely impairs vision and can lead to blindness. LSCD causes include chemical burns, infections, multiple previous operations and congenital malformations. Allogeneic limbal transplantation is a procedure for treating LSCD where prepared limbal tissue is attached using a double running suture during allogeneic penetrating keratoplasty (PKP). A total of 22 patients underwent ALT surgery between February 2019 and June 2022 at the University Hospital Halle (Saale). Regular follow-up was performed postoperatively every three months and included visual acuity testing, pressure measurement, slit lamp microscopic examination, fundoscopy, corneal topography and anterior segment optical coherence tomography (AS-OCT). The mean patient age was 69.5 years, and the mean follow-up was 19 months. All included patients had LSCD and multiple previous surgeries. Patient LSCD etiology was 59% infectious and 41% traumatic. ALTs integrated into corneal surfaces in all patients, demonstrated on AS-OCT. Since most patients initially received allogeneic limbal transplants, none of the operated eyes had surgical complications. Overall, visual acuity improved postoperatively from an initial 2.06 to 1.44 logarithm of the minimum angle of resolution (logMAR). Allogeneic limbal transplantation can be used to treat LSCD and its integration into the surrounding corneal tissue can be observed on AS-OCT.

Concrements of the Lacrimal Apparatus. / Konkremente des Tränenapparates.

Concrements of the lacrimal apparatus, known as dacryoliths, can occur at different localizations and can cause a variety of symptoms. A common clinical sign is chronic inflammation, possibly exhibiting acute exacerbation. Based on a literature review and descriptive clinical cases with histopathological correlations, this contribution summarises the most important information concerning epidemiology, aetiopathogenesis, composition, histology, and therapy of lacrimal concrements. Furthermore, factors known to affect lacrimal lithogenesis are addressed. Concrements of the lacrimal gland cause a swelling at the lateral canthus. With only mild pain, this manifests as circumscribed conjunctival hyperaemia. Histologically, the gland tissue is characterised by acute-erosive to chronic inflammation. The concrements consist of amorphic material. Inflammatory infiltration is dominated by neutrophil granulocytes. Canalicular concrements are highly correlated with chronic canaliculitis. Besides epiphora, patients present with purulent discharge at the affected canaliculus. Actinomyces are frequently found inside these deposits and form drusen-like formations. The surrounding tissue reacts with plasma-cellular and granulocytic inflammation. Dacryoliths (concrements of the lacrimal sac) are associated with dacryocystitis, whereby acute and chronic types are common. Stones can be found in up to 18% of patients undergoing dacryocystorhinostomy or dacryoendoscopy. Preoperative diagnostic testing is challenging, as many lacrimal sac stones cannot be reliably visualised by diagnostic procedures. Recurring episodes of epiphora, mucopurulent discharge, and dacryocystitis are common indicators of dacryoliths. Lacrimal syringing is often possible and shows that total blockage is not present. Histology of the lacrimal mucosa reveals lymphocytic infiltration and submucosal fibrosis. The immediate vicinity of the dacryoliths shows acute inflammation. Therapy consists of stone extraction and improving lacrimal drainage, as the latter is recognised as the main risk factor for dacryolith formation.

Retinal Vascular Occlusion after COVID-19 Vaccination: More Coincidence than Causal Relationship? Data from a Retrospective Multicentre Study.

BACKGROUND: To investigate whether vaccination against SARS-CoV-2 is associated with the onset of retinal vascular occlusive disease (RVOD). METHODS: In this multicentre study, data from patients with central and branch retinal vein occlusion (CRVO and BRVO), central and branch retinal artery occlusion (CRAO and BRAO), and anterior ischaemic optic neuropathy (AION) were retrospectively collected during a 2-month index period (1 June-31 July 2021) according to a defined protocol. The relation to any previous vaccination was documented for the consecutive case series. Numbers of RVOD and COVID-19 vaccination were investigated in a case-by-case analysis. A case-control study using age- and sex-matched controls from the general population (study participants from the Gutenberg Health Study) and an adjusted conditional logistic regression analysis was conducted. RESULTS: Four hundred and twenty-one subjects presenting during the index period (61 days) were enrolled: one hundred and twenty-one patients with CRVO, seventy-five with BRVO, fifty-six with CRAO, sixty-five with BRAO, and one hundred and four with AION. Three hundred and thirty-two (78.9%) patients had been vaccinated before the onset of RVOD. The vaccines given were BNT162b2/BioNTech/Pfizer (n = 221), followed by ChadOx1/AstraZeneca (n = 57), mRNA-1273/Moderna (n = 21), and Ad26.COV2.S/Johnson & Johnson (n = 11; unknown n = 22). Our case-control analysis integrating population-based data from the GHS yielded no evidence of an increased risk after COVID-19 vaccination (OR = 0.93; 95% CI: 0.60-1.45, p = 0.75) in connection with a vaccination within a 4-week window. CONCLUSIONS: To date, there has been no evidence of any association between SARS-CoV-2 vaccination and a higher RVOD risk.

ALT (allogeneic limbal transplantation): a new surgical technique for limbal stem cell deficiency.

PURPOSE: Limbal stem cell deficiency (LSCD) is a rare but extremely relevant disease of the eye. LSCD patients often require a variety of surgical procedures, including keratoplasty in some cases. However, the outcome of these surgeries, including opacification and revascularization, is often frustrating due to LSCD relapse. METHODS: We developed a new surgical technique for the treatment of LSCD in which partial allogenic limbal transplantation (ALT) is carried out as part of penetrating keratoplasty (PK). After the PK, 1-8 slices from the limbal tissue of the donor graft are prepared and placed under the double running sutures attaching the corneal graft. This procedure was performed on 14 patients with LSCD, caused by severe ocular burn in 5 cases and by infection in 9. Between one and eight limbal transplants were used depending on the extension of the LSCD. RESULTS: All 14 patients showed stable or increased visual acuity after the ALT surgery compared to their preoperative visual acuity. All of the grafts were integrated into the superficial corneal layers without progression of corneal vascularization beyond the limbal grafts. The median follow-up period was 12 months on average. CONCLUSION: The ALT method seems to be a promising surgical procedure for the treatment of patients with LSCD. It can be properly carried out in the context of keratoplasty and does not require a separate donor tissue. The ALT grafts may offer the possibility of constructing a new limbal region, resulting in stable or even increased visual acuity and the absence of corneal vascularization.

New Safety Aspects in Corneal Donation-Studies on SARS-CoV-2-Positive Corneal Donors.

In the tissue donation field, to prevent pathogen transmission, all donors are screened by postmortem swabs for SARS-CoV-2 using qRT-PCR. Corneas from donors who tested positive for SARS-CoV-2 were subjected to further investigations. Corneal transplants and culture medium from positive donors were cultured under appropriate safety conditions for further analyses. Cornea tissue samples, including sclera/limbus/cornea, and culture media were taken at different time points for testing for SARS-CoV-2 using qRT-PCR, immunohistochemistry (IHC) and subgenomic RNA (sgRNA) analysis. Between January and May 2021, in four donors with initial negative premortem rapid tests, SARS-CoV-2 was detected post-mortem using qRT-PCR. In these cases, SARS-CoV-2 was observed at the beginning of cultivation in both tissue and culture medium using qRT-PCR and IHC. The virus was mainly localized in the limbus epithelial cells, with a stable detection level. Premortem rapid tests are potentially insufficient to exclude SARS-CoV-2 infection in corneal donors. While, for SARS-CoV-2, the risk of infection via transplants is considered low, a residual risk remains for presymptomatic new infections. However, our investigations provide the first indications that, with organ cultures, the risk of virus transmission is minimized due to the longer minimum culture period.

Impact of the transcription factor IRF8 on limbal epithelial progenitor cells in a mouse model.

The limbus of the eye is the location of the corneal epithelial stem cell niche. These cells are necessary for continuous renewal of the corneal epithelium. In the case of limbal stem cell deficiency, these cells are damaged, and the whole cornea becomes opaque. It is important to be able to identify stem cells that could be applied for new therapeutic strategies. There are various known markers to characterize these cells, including p63, Nanog, oct4 and FGFR2. However, none of these markers are exclusively expressed in these stem cells (they are also expressed in transient amplified cells). It seems likely that a combination of stem cell markers will be necessary for corneal stem cell identification. The aim of this study was to detect IRF8 in limbal epithelial stem cells and to determine its function. In a mouse model, IRF8 could be detected in limbal and basal epithelial cells of the cornea by histological and immunohistological staining of wild-type mouse eyes. Furthermore, the limbus of the eye was significantly smaller in IRF8-knockout mice than in wild-type mice, and the expression of Nanog was lower in IRF8-knockout mice. This suggests that IRF8 has an influence on the maintenance of stem cell properties in the limbus, possibly by affecting the expression of Nanog. Furthermore, IRF8 has an impact on E-cadherin and N-cadherin expression in the mouse eye.

Posttraumatic Ocular Hypotony Through Epithelial Downgrowth. / Posttraumatische Bulbushypotonie durch Epithelinvasion.

BACKGROUND: Intraocular epithelial downgrowth is a rare but potentially devastating posttraumatic complication. If left untreated, this may result in corneal decompensation, secondary angle-closure glaucoma, retinal detachment and blindness. PATIENT AND METHOD: A 10-year-old patient with penetrating globe injury and delayed wound management elsewhere presented with corneal melting and decompensation, retinal detachment and ocular hypotony. Following penetrating keratoplasty, cyclopexy and vitrectomy, corneal melting in the interface with renewed retinal detachment was noted within days. The hopeless prognosis required enucleation of the globe. RESULTS: Optical coherence tomography revealed not only corneal melting, but also markedly hyperreflective structures posterior to the cornea. Immunohistology demonstrated diffuse multi-layered nonkeratinised squamous cell epithelium on the posterior corneal surface, iris, ciliary bodies, and retina, as well as below the choroid, with renewed tractional retinal detachment. CONCLUSION: Posttraumatic epithelial downgrowth may result in tractional retinal detachment, cyclodialysis cleft and/or corneal melting. Hyperreflective membrane deposits on OCT may be indicative of diffuse epithelial downgrowth. Especially in children, prompt wound closure in globe injuries is vital to avoid this serious posttraumatic complication.