[Modified mini-SLET for treatment of complex cases in pterygium surgery]. / Modifizierte Mini-SLET zur Behandlung von komplexen Fällen in der Pterygiumchirurgie.

BACKGROUND: The major problem associated with the benign but destructive growing pterygium is the high recurrence rate. A new surgical technique to lower recurrence rates is minor ipsilateral simple limbal epithelial transplantation (mini-SLET), where the regeneration potential of limbal stem cells is used in combination with amniotic membrane transplantation (AMT) for surgical reconstruction. The aim of this study is to assess the surgical outcome of the mini-SLET technique with tenonectomy, mitomycin C, and AMT as used in the authors' hospital. MATERIALS AND METHODS: A total of 16 eyes from 15 patients undergoing mini-SLET after surgical pterygium removal with tenonectomy, mitomycin C, and AMT were analyzed retrospectively. Two different groups of pterygia were enrolled: group 1 included recurrent pterygia (n = 10) and group 2 comprised primary large pterygia such as double-head pterygia (n = 6). In addition to assessment of best corrected visual acuity and compete ophthalmological examination, preoperative slip-lamp examination with photo documentation served to calculate the corneal size of the pterygium head using VISUPAC software (Zeiss, Oberkochen, Germany). Postoperatively, best corrected visual acuity and slit-lamp examination were routinely evaluated. The surgical outcome was defined by the postoperatively achieved best corrected visual acuity, restoration of the ocular surface, recurrence rate, and rate of postoperative complications. RESULTS: Median follow-up in all patients was 27 months; in groups 1 and 2 it was 30.7 and 25.3 months, respectively. No recurrence developed in 15 eyes (93.75%). Only one group 1 patient (6.25%) suffered a recurrent lesion after 10 months. Postoperatively, logMAR visual acuity did not change significantly. During follow-up, complications were limited to one case of early wound dehiscence. CONCLUSION: Mini-SLET in combination with tenonectomy, mitomycin C, and AMT enables good surgical reconstruction of the ocular surface, and almost complete healing in the sense of restitutio ad integrum is possible. The results of the present study have shown the technique's effectiveness for recurrence prevention.

Comparison of Bleb Morphology following PRESERFLO® MicroShunt and Trabeculectomy Using Anterior Segment OCT.

Trabeculectomy has traditionally been upheld as the gold standard in glaucoma surgery, but recent advancements, including the PRESERFLO® MicroShunt, have introduced less invasive techniques to mitigate complications and reduce intraocular pressure (IOP). The examination of bleb morphology post-filtering surgery is critical for modulating wound healing and ensuring long-term success. While previous evaluations of PRESERFLO-generated blebs have relied on data from trabeculectomy blebs, the differing surgical techniques used in PRESERFLO and trabeculectomy surgeries suggest potential variations in bleb morphologies. This study conducted a comparative analysis of blebs resulting from PRESERFLO and trabeculectomy procedures. Retrospective descriptive assessments using the Jenaer Bleb Grading System were performed, along with quantitative evaluation using eight-dimensional parameters utilizing anterior segment OCT. We included 93 eyes (57 following PRESERFLO, 36 following trabeculectomy). In the descriptive assessment, PRESERFLO-generated blebs exhibited fewer conjunctival cysts (3.5% vs. 22.2%, p = 0.007) and cavernous changes (10.5% vs. 30.5%, p = 0.021) compared to trabeculectomy. Quantitatively, overall bleb dimensions were comparable (maximal bleb height, width, and length, p > 0.05 for all). However, PRESERFLO blebs displayed a shallower (0.52 ± 0.24 vs. 0.67 ± 0.3 mm, p = 0.017) yet longer (4.12 ± 1.54 vs. 3.23 ± 1.64 mm, p = 0.024) episcleral lake. A thicker bleb wall (1.52 ± 0.46 vs. 1.10 ± 0.37 mm, p < 0.001) along with more posteriorly positioned blebs (distance to limbus = 6.16 ± 1.36 vs. 4.87 ± 1.34 mm, p < 0.001) were observed following PRESERFLO. This study illuminates the nuanced morphological differences between PRESERFLO and trabeculectomy blebs. Understanding these distinctions is vital, empowering clinicians to make informed postoperative decisions and avoid misinterpretation of bleb morphology.

Factors Correlated With Mid-Term Morphology of Functional Blebs Following Implantation of Preserflo MicroShunt Using AS-OCT.

Purpose: Evaluating bleb morphology is crucial after glaucoma filtering surgery. Advances in anterior segment optical coherence tomography (AS-OCT) allow for objective assessment. While various parameters differentiate functional from failed blebs, limited information exists regarding variations within functional blebs. This study aimed to identify factors influencing morphology of functional blebs following implantation of Preserflo MicroShunt. Methods: Eyes with functional blebs after Preserflo were retrospectively included. Age, gender, lens status, preoperative intraocular pressure (pre-IOP) and number of glaucoma medications were documented along with biometric measurements as axial length (AL), white-to-white distance, and anterior chamber depth. Postoperative data included time elapsed since surgery (TaS) and postoperative IOP (post-IOP). Bleb dimensions were measured using AS-OCT including maximal bleb height (MBH), width, length (MBL), bleb wall thickness (BWT), and bleb distance to limbus (DtL) along with dimensions of episcleral lake (maximal height, width [MLW], and length). Linear regression models were applied to correlate these parameters with bleb dimensions. Results: Included were 50 eyes from 50 patients. Mean IOP decreased from 25.3 ± 10.0 to 11.9 ± 3.0 mm Hg after 278.5 ± 221.9 days after surgery. MBH correlated negatively with age (unstandardized coefficients [uSC] = -0.012) and TaS (uSC = -0.001, P = 0.008 for both). BWT correlated negatively with age (uSC = -0.013, P = 0.02), MBL with AL (uSC = -0.566, P = 0.01) and MLW with pre-IOP (uSC = -0.073, P = 0.02). DtL exhibited a positive correlation with post-IOP (uCS = 0.136, P = 0.02). Conclusions: Morphology of functional blebs might be influenced by multiple factors such as age, TaS, AL, and pre- and post-IOP. Translational Relevance: Age, time after surgery, axial length, and preoperative and postoperative IOP could affect the morphology of a functional bleb; hence, these factors should be taken into consideration when making treatment decisions.

Results of open bleb revision as management of primary bleb failure following XEN 45 gel stent and Preserflo™ Microshunt.

PURPOSE: The success of filtering surgery as in XEN-Gel-Stent (XEN) and Preserflo-Microshunt (PF) depends mainly on a functioning bleb. Primary bleb failure (PBF) is not uncommon and can be treated with needling or open bleb revision (OBR). The aim of the study is to compare surgical outcomes of OBR after XEN and PF. METHODS: Eyes which received OBR as management of PBF following implantation of XEN or PF were retrospectively included. Intraocular pressure (IOP), number of IOP lowering medications (NoM), and success rates (SR) were compared between groups. Complete and qualified success were defined as IOP ≤18mmHg and a reduction of >20%, without and with medications, respectively. RESULTS: 29 eyes after XEN and 23 eyes after PF were included. Six months following OBR, IOP reduced from 24.2±4.7 to 13.5±4.6 after XEN and from 27.3±8.7 to 15.9±5.8mmHg after PF (both p<0.001). NoM did not change (0.7±1.3 to 0.4±0.8 after XEN and 1.2±1.3 to 1.0±1.5 after PF, p>0.05 for both). Complete SR were higher after XEN than after PF (58.6% vs. 30.4%, p=0.04). Complications were mild and managed mainly conservatively. Additional glaucoma surgery was needed in 17% and 30% of eyes after XEN and PF, respectively (p=0.26). CONCLUSION: Although OBR was effective as management of PBF following XEN and PF, SR were higher after XEN than after PF along with comparable safety profile. The change of the surgical approach from ab interno during XEN-Implantation to ab externo during OBR seems to enhance SR compared to PF, where both interventions are done ab externo.

A Comparative Analysis of Morphology and Dimensions of Functional Blebs following PRESERFLO-Microshunt and XEN-Gel-Stent, a Study Using Anterior Segment OCT.

Evaluation of bleb morphology is a vital part of successful filtration glaucoma surgery. The PRESERFLO-MicroShunt (PRESERFLO) and XEN-Gel-Stent (XEN) are drainage devices implanted using different surgical approaches (ab externo and ab interno, respectively), potentially resulting in distinct bleb morphology. Understanding these morphological differences is essential for postoperative care. In this study, we retrospectively examined functioning blebs following PRESERFLO and XEN implantation using high-resolution anterior segment OCT imaging. Qualitative assessment utilizing the Jenaer Bleb Grading System and quantitative assessment measuring 12 parameters representing bleb dimensions were conducted, and the results were compared between the two groups. A total of 80 eyes from 80 patients were included (41 after PRESERFLO, 39 after XEN). Functioning blebs following PRESERFLO exhibited a higher frequency of hyperreflective tenon changes compared to XEN (31.7% vs. 10.3%, respectively, p = 0.02) and a lower frequency of cavernous changes (17.1% vs. 35.9%, p = 0.05). Additionally, PRESERFLO blebs showed a higher frequency of visible episcleral lakes (92.7% vs. 30.8%, p < 0.001). Furthermore, PRESERFLO blebs demonstrated larger height (2.13 ± 0.5 vs. 1.85 ± 0.6 mm, p = 0.03), width (10.31 ± 2.3 vs. 9.1 ± 2.3 mm, p = 0.02), length (9.13 ± 1.8 vs. 8.24 ± 1.9 mm, p = 0.04), posterior location relative to the limbus (6.21 ± 1.2 vs. 5.21 ± 1.8 mm, p = 0.005), and a thicker bleb wall (1.60 ± 0.5 vs. 1.1 ± 0.4 mm, p = 0.004). Functioning blebs following PRESERFLO and XEN displayed morphological distinctions, likely attributed to variations in surgical techniques (ab externo vs. ab interno) and stent dimensions. These morphological differences should be taken into consideration when evaluating blebs, as they could impact assessments of bleb functionality and influence decisions regarding postoperative interventions.

Current Practice in the Treatment of Epithelial and Melanocytic Tumours with Interferon-α2b: A Survey of Tertiary Eye Centres in Germany.

PURPOSE: To evaluate the standard of care, in particular the use of topical or subconjunctival interferon-α2b, in treating ocular surface squamous neoplasia or melanocytic tumours in tertiary eye centres in Germany. METHODS: A survey containing 14 questions was sent to 43 tertiary eye centres in Germany. The questions addressed the surgical and medical management of ocular surface squamous neoplasia and melanocytic tumours (primary acquired melanosis and malignant melanoma), as well as the clinical experiences and difficulties in prescribing off-label interferon-α2b eye drops and subconjunctival injections. RESULTS: Twenty-four tertiary eye centres responded to the survey. Eighty-three percent of centres had used interferon-α2b in their clinical practice and 25% prescribed it as the first-line cytostatic agent following surgical excision of ocular surface squamous neoplasia, while 10% would do so for melanocytic tumours. Correspondingly, the majority of respondents selected mitomycin C as their first-line agent. Side effects were uncommon with topical interferon-α2b eye drops but were more frequently reported after subconjunctival interferon-α2b injections. In total, eight centres had experience with interferon-α2b injections. The most significant obstacles perceived by ophthalmologists when prescribing interferon-α2b were its high cost and the reimbursement thereof. CONCLUSION: Off-label mitomycin C was the preferred adjuvant therapy for epithelial and melanocytic tumours, with interferon-α2b being the standard second-line option. Interferon-α2b has predominantly been used to treat ocular surface squamous neoplasia and, to a lesser extent, melanocytic tumours at German tertiary eye centres. Following its market withdrawal, supply shortages of interferon-α2b are likely to have a profound impact on patient care and their quality of life.

Brachytherapy as a curative option for ocular surface squamous neoplasia.

PURPOSE: Ocular surface squamous neoplasia (OSSN) has a high recurrence rate if only treated with surgical excision, especially in cases with positive excision margins. To reduce recurrence, we used brachytherapy after surgical excision for limbal and bulbar lesions in addition to chemotherapy/immunotherapy, cryotherapy, or external beam radiotherapy as adjunctive or primary therapies. METHODS: Nine eyes with isolated OSSN lesions were included in the study. Adjunctive brachytherapy with Ruthenium106-plaques was administered. The follow-up included regular biomicroscopic slit-lamp examination and photo-documentation. Additionally, a staging check for metastasis was performed in cases with squamous cell carcinoma (SCC). RESULTS: The average age of patients at the time of presentation was 66 ± 12 years. Follow-up time was 52.8 ± 44.6 months. The maximal tumour base varied between 3 and 28 mm. SCC was confirmed by histology in all cases. No recurrences were recorded during the follow-up, and organ salvage and eye function preservation were achieved. Radiotherapy-induced complications included secondary glaucoma (n = 1) and scleral melting (n = 1). Other complications, such as radiogenic retinopathy, were not observed. CONCLUSION: Brachytherapy with Ruthenium106-plaques offers an additional option for adjunct treatment of limbal and bulbar OSSN presenting with only a focal spread. Organ salvage can be achieved with a low complication rate and recurrence-free survival. This technique offers globe salvage in patients with tumours involving intraocular infiltration.

[Bleb morphology using optical coherence tomography : After primary implantation of XEN gel stent and open conjunctival revision]. / Morphologie des Sickerkissens mittels optischer Kohärenztomographie : Nach primärer Implantation von XEN-Gel-Stent und offener Bindehautrevision.

BACKGROUND: The implantation of a XEN gel stent is an innovative method for filtration surgery using an ab interno approach. The morphological evaluation of the resulting bleb is decisive for surgical success. Bleb revision is frequently needed after XEN implantation and might affect the bleb morphology. Aim of this study was to examine bleb morphology using anterior segment OCT (AS-OCT) and analyze the morphological differences of blebs after primary XEN implantation and after bleb revision. MATERIAL AND METHODS: Included were eyes that underwent XEN implantation (Pr-X) or bleb revision after XEN (Re­X group). An AS-OCT of blebs was performed and images were classified using a novel classification system (the Jenaer bleb grading system, JBGS). Frequency of different tomographic patterns (M) and their correlation with intraocular pressure (IOP) were analyzed. RESULTS AND DISCUSSION: A total of 69 eyes (40 in the Pr­X and 29 in the Re­X groups) were included. At the conjunctival level, the most common M in both groups was subconjunctival spaces (M-C2) followed by intraconjunctival cysts (C1) and no conjunctival changes (C0). No differences of frequencies between the two groups or of IOP between the three Ms were seen. At the tenon level, the most commonly seen Ms in the Pr­X group were hyporeflective and cavernous changes (M-T2, T3) followed by no changes (M0) and hyperflective changes (T1). In the Re­X group, the M­T1 and T2 were most commonly seen followed by T3 and T0. The M­T2 and T3 in the Pr­X group and the M­T1 and T2 in the Re­X group correlated with lower IOP. An episcleral lake (M-ES1) was seen significantly less frequently in the Pr­X group compared with Re­X group where it correlated with lower IOP CONCLUSION: The hyperreflective changes at the tenon level and the presence of an episcleral lake were seen more frequently following bleb revision compared with primary XEN implantation and correlated with lower IOP. The interpretation of bleb morphology using AS-OCT should only be done considering the surgical approach used.

Midterm results of conjunctival reconstruction with buccal mucosa and amniotic membrane after resecting ocular surface squamous neoplasia of the fornix.

OBJECTIVE: To evaluate the midterm results of tumour resection with or without adjunctive therapy for ocular surface squamous neoplasia of the fornix, including conjunctival reconstruction with buccal mucosa and amniotic membrane. METHODS: A retrospective case-series analysis including slit-lamp examination, photographic documentation, and biopsy results (repeated when clinical findings changed). Analysis centred on eye function, complications, additional procedures, and recurrence rate. Surgical technique included tumour resection and subsequent reconstruction of lost conjunctiva with buccal mucosa and amniotic membrane. RESULTS: We included 83 affected eyes from 76 patients (mean age, 63.10 ± 14.45 years; 34 females) seen over a mean follow-up period of 26.56 ± 21.17 months. We achieved bulbus oculi salvage in 82 eyes (98.79%) and typically preserved visual acuity (mean 0.2 ± 0.5 logMAR and 0.3 ± 0.5 logMAR at presentation and last follow-up, respectively). Moreover, only 23 patients (27.71%) required corrective surgery for clinically relevant complications. The main complications included symblepharon (9.64%; n = 8), cicatricial ectropion (9.64%; n = 8), pannus (9.64%; n = 8), and corneal decompensation (8.43%; n = 7). Local tumour recurrence was seen in 23 patients (27.71%). CONCLUSIONS: These midterm results confirm the efficacy of conjunctival reconstruction with amniotic membrane and buccal mucosa after resection of ocular surface squamous neoplasia from the fornix with palpebral and bulbar conjunctiva involvement. We not only achieved good tumour control and organ salvage with high levels of organ preservation but we also achieved good functional outcomes and acceptable recurrence rates. All clinically significant complications could be corrected in separate procedures.

Changes of retinal oxygen saturation during treatment of diabetic macular edema with a pre-defined regimen of aflibercept: a prospective study.

PURPOSE: To study the effect of anti-VEGF therapy for diabetic macular edema (DME) on retinal oxygen saturation (O2S) and its correlation with functional and anatomical changes of retinal tissue. METHODS: An interventional prospective single group study. Included were 10 eyes of 10 patients with visually significant DME which received a fixed regimen of intravitreal aflibercept every 4 weeks for 5 months, followed by 3 injections every 8 weeks, and were controlled monthly. Visual acuity (VA), central retinal thickness (CRT), arterial (aO2S), venous (vO2S) and arterio-venous difference (AVdO2S) retinal oxygen saturation were noted monthly. Changes after 5th (V6) injection and on last follow-up (V12) were studied. Correlations of different parameters were analyzed. RESULTS: The aO2S did not change whereas vO2S decreased (62.2 ± 9.4 pre-op to 57.2 ± 10.5 on V6, p = 0.03). This remained unchanged at 59.4 ± 13.2 on V12 (p = 0.2) and was accompanied by an increase of AVdO2S (40.8 ± 8.3 pre-op to 44.8 ± 10.6, p = 0.03 on V6) which was followed by a non-significant decrease to 41.8 ± 11.3 on V12 (p = 0.06). We found no correlation between BCVA and aO2S. However, mild correlation between BCVA and both vO2S and AVdO2S (r = -0.2 p = 0.035 and r = 0.185 p = 0.05 respectively) was found. No correlation was found between CRT and aO2S, vO2S, or AVdO2S. CONCLUSIONS: During DME treatment with fixed regimen of intravitreal aflibercept over 11 months, we observed a reduction of vO2S and increase of AVdO2S which correlated with BCVA but not CRT. This could be explained by increasing consumption of O2S in the central retina and, possibly, by re-perfusion process.

Bowel Obstruction After Sacrocolpopexy: A Case Series.

OBJECTIVES: Bowel obstruction after sacrocolpopexy (SC) can cause significant morbidity. The aim of this study was to delineate clinical and surgical factors associated with bowel obstruction after SC and to describe its presentation, management, and sequelae. METHODS: We performed a retrospective case series of patients who underwent open, laparoscopic, or robotic SC within a large health maintenance organization and a single academic medical center between January 1, 2009, and December 31, 2019. RESULTS: Of 3,231 patients who underwent SC, 32 (1.0%) experienced a bowel obstruction. Sacrocolpopexy was performed laparoscopically or robotically in 19 (59.4%) and abdominally in 13 (40.6%). The mean time to bowel obstruction was 1.9 years (SD, 2.5; range, 3 days to 8.8 years). In patients who experienced bowel obstruction, medical management was undertaken in 19 (61.3%) cases. Eight of the 13 (61.5%) surgically managed cases underwent bowel resection, and 3 cases (23.1%) reported partial mesh excision. Recurrent obstruction was seen in 2 (10.5%) of the medically managed and 2 (15.4%) of the surgically managed cases. CONCLUSIONS: Bowel obstruction is a rare complication of SC and our rate of at least 1.0% corroborates those in the literature. Obstruction occurs from days to years after SC. Nonsurgical management was effective in most cases, with low rates of recurrent obstruction. In surgically managed cases, the majority included bowel resection or mesh excision; however, mesh excision was not associated with a subsequent identifiable procedural intervention for recurrent prolapse. These data inform patient counseling and surgical planning before SC and aid in diagnosis and management of bowel obstruction after SC.

Partial descemetorhexis for delayed Descemet membrane detachment following penetrating keratoplasty, suggestion of a pathomechanism.

PURPOSE: to report a case of delayed Descemet membrane detachment (DMD) 45 years after penetrating keratoplasty (PK) for keratoconus and its management with a partial descemetorhexis after failed air/gas descemetopexy. A pathomechanism of DMD is proposed based on the anatomic appearance of the DMD and the success of descemetorhexis. OBSERVATIONS: a 60-year old male presented with acute corneal edema of his left eye 45 years after successful PK for keratoconus. Anterior segment ocular coherence tomography (AS-OCT) revealed a wide area of DMD without a visible tear. Reattachment was tried using air and gas descemetopexy with only temporary success. A partial descemetorhexis was then performed just centrally to the graft-host interface and only in the detached area followed by injection of gas bubble. Complete reattachment of Descemet membrane (DM) on the 1st post-operative day was achieved. This anatomical success was maintained 3 months post-surgery and accompanied by decrease of central corneal thickness, however with uncomplete restoration of visual acuity. CONCLUSION: delayed DMD following KP for keratoconus should be differentiated from acute graft rejection. It could be a result of Descemet tear, but in some cases and despite careful observation of AS-OCT no tear could be seen. In such cases, a tractional detachment of DM might be the underlying pathomechanism and descemetorhexis could help manage it. This new surgical approach might help avoid a re-keratoplasty. IMPORTANCE: This is the first case report describing success of partial descemetorhexis as a surgical management option for delayed DMD and suggesting a pathogenesis based on this success. This might help avoid re-keratoplasty as a management of this rare complication.

Proton radiotherapy in advanced malignant melanoma of the conjunctiva.

BACKGROUND: The management of conjunctival melanoma is challenging and frequently ends in exenteration. The aim of this retrospective study was to evaluate the long-term results of proton beam radiation with regard to various clinical parameters. METHODS: Eighty-nine patients with extended conjunctival melanoma (≥T2) and multifocal bulbar located tumors (T1c/d) were treated consecutively with proton radiotherapy (dose 45 Gy). The following parameters were assessed: TNM stage, tumor origin, local recurrence, performance of exenteration, occurrence of metastases, overall survival, and potential complications. A time-to-event analysis was preformed to the primary endpoints: relapse, metastasis, exenteration, and death by use of Kaplan-Meier cumulative survival estimates and Cox proportional hazards regression that provides hazard ratios and 95% confidence intervals. RESULTS: The median follow-up time was 4.2 years (max. 21.7 years). Local recurrence and metastatic disease occurred in 33% and 16% of patients, respectively. Exenteration-free survival and overall survival tended to be worse in T3 melanoma. No association between tumor origin and local recurrence, metastatic disease, or overall survival was observed. Main complications after proton radiotherapy were sicca-syndrome (30%), secondary glaucoma (11%), and limbal stem cell deficiency (8%). CONCLUSIONS: In summary, proton radiotherapy in conjunctival melanoma is an effective alternative to exenteration, with a 5-year cumulative probability of eye preservation of 69%.

Pretreatment Diagnosis of the Small Renal Mass: Status of Renal Biopsy in the United States of America.

INTRODUCTION: We surveyed United States of America-based urologists to characterize practice patterns and indications to perform a renal mass biopsy for small renal masses. MATERIALS AND METHODS: Members of the American Urological Association who practice in the United States were invited to participate in a 11-question web-based survey that was distributed via SurveyMonkey® from December 2016 to January 2017. RESULTS: There were 1131 respondents. The respondents equally represented all regions of the United States; the majority were in private practice. Overall, 32% of American urologists would "never" perform a biopsy of a renal mass ≤4 cm. Those who saw fewer than five small renal masses per year were more likely to "never" perform a renal biopsy on either a renal mass ≤4 cm or a renal mass 2-3 cm compared with those who saw more than five small renal masses per year (p < 0.001). Urologists who practiced at an academic hospital were more likely to perform a renal biopsy on both a renal mass ≤4 cm and a renal mass 2-3 cm compared with private practice and government-based urologists (p < 0.001 and p = 0.008 respectively). The primary reason for not performing a biopsy, cited by 68% of responding urologists, was that the results of a biopsy "would not change their management of the renal mass." Respondents independently performed only 2% of biopsies; however, almost half stated that they would be interested in learning office-based ultrasound-guided biopsy of a small renal mass. CONCLUSIONS: Among members of the American Urological Association, biopsy of a small renal mass remains an underutilized diagnostic procedure, especially in light of 6000 unnecessary surgeries annually; nonuniversity-based urologists and those who see <5 renal mass cases each year infrequently perform a biopsy. Currently, interventional radiologists perform almost all small renal mass biopsies.

[Rehabilitation Following Limbal Stem Cell Deficiency: Current Treatment Options and Future Developments]. / Optische Rehabilitation nach Limbusstammzellinsuffizienz: aktuelle Behandlungsmöglichkeiten und Entwicklungen.

Limbal stem cell deficiency (LSCD) is a condition caused by the loss of corneal epithelial regenerative potential. The treatment of this condition is still a challenge. It results from various conditions both intrinsic as well as extrinsic. LSCD can be either uni- or bilateral and either partial or total. Today treatment options include a variety of techniques including transplantation of amniotic membrane and limbal tissue or tissue engineered cell sheets. This article summarizes the current techniques to treat LSCD and upcoming developments.

Clinical outcomes of amniotic membrane transplantation in the management of acute ocular chemical injury.

BACKGROUND: Amniotic membrane transplantation (AMT) has been used in the management of acute ocular chemical burns to promote epithelialisation, reduce inflammation and restore ocular surface integrity. The aim of this study is to analyse the morphological and functional outcomes of patients receiving AMT after ocular chemical burn. METHODS: We performed a retrospective analysis of all patients treated for acute ocular chemical burn between 1998 and 2008 in two participating centres (University of Duisburg-Essen, Germany and Royal Victoria Infirmary, Department of Ophthalmology, Newcastle University, UK). Ocular chemical burns were classified by Roper-Hall and Dua classifications. RESULTS: 72 eyes of 54 consecutive patients aged 37.3 years (±SD 11.6 years) were included in this cohort study. 7 chemical burns were acid burns, 61 were alkaline and 4 were of unknown origin. In 37 eyes (51.4%), AMT was applied within the first 6 days after injury. Mean follow-up time was 36.4 months (median 18.5; 1.3-117.3  months). Overall, 29 eyes (40.3%) achieved a best-corrected visual acuity of LogMAR 0.2 (0.63 decimal) or better at final visit. Complete 360° limbal stem cell deficiency (LSCD) occurred in 33 eyes (45.8%), while partial LSCD occurred in 21 eyes (29.2%). CONCLUSION: AMT is an effective adjunctive treatment in the management of acute ocular chemical burns to support epithelial healing and restore ocular surface integrity with potential to improve vision. However, long-term debilitated vision remained in those with severe burns complicated by LSCD.

Frequent TERT Promoter Mutations in Ocular Surface Squamous Neoplasia.

PURPOSE: Ocular surface squamous neoplasia, including intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma (SCC), are one of the most common malignant tumors of the conjunctiva. Little is known of the genetic alterations involved in their pathogenesis. Promoter mutations in telomerase reverse transcriptase (TERT) have been identified in various cancers, including many associated with ultraviolet (UV) exposure. Our study analyzes the mutation rate and clinicopathological associations of TERT promoter mutations in ocular surface squamous neoplasia. METHODS: DNA was isolated and the region of the TERT promoter where hotspot mutations can occur analyzed by Sanger-sequencing in 48 ocular surface squamous neoplasia tumor samples (6 CIN and 42 SCC). An analysis of associations between TERT promoter mutation status and various clinicopathological parameters was performed. RESULTS: We identified TERT promoter mutations in 21 of 48 ocular surface squamous neoplasia samples (43.8%), including 4 in CIN and 17 in SCC. The mutations consisted of 8 Chr.5:1295228C>T, 1 Chr.5:1295228_1295229CC>TT, 5 Chr.5:1295242_1295243CC>TT, and 12 Chr.5:1295250C>T mutations. All mutations were C>T or CC>TT alterations, demonstrating a UV-signature. TERT promoter mutations showed no statistically significant associations with clinicopathological parameters. CONCLUSIONS: Telomerase reverse transcriptase promoter mutations are found in almost half of ocular surface squamous neoplasias and have a mutation profile supporting UV induction as the major source of mutagenesis. We conclude that UV induced TERT promoter mutations leading to aberrant overexpression of telomerase is a major pathogenetic factor in ocular surface squamous neoplasia.

Establishment of a Cell Line From Conjunctival Squamous Cell Carcinoma: PeCa-UkHb-01.

PURPOSE: Until now, no epithelial cell line from conjunctival squamous cell carcinoma (SCC), to our knowledge, has existed; therefore, the establishment of a model cell line would be a useful tool for further studies. In particular, the phenotypic and molecular characterization in comparison to other SCC cells is of high interest because this would enable the development of new treatment options for clinical application in ophthalmic oncology. METHODS: Epithelial cells were isolated from a bulbar conjunctiva SCC obtained from a 74-year-old male, harvested by stepwise trypsinization and named PeCa-UkHb-01. Cell doubling and the number of passages were determined. Short tandem repeats (STR) and karyotype analyses were performed. Semiquantitative real-time PCR and immunocytochemical fluorescence staining were carried out to detect tumor and epithelial cell markers. RESULTS: The cells had an epithelial and conjunctival phenotype. They grew above passage number 50 in a doubling time at approximately 34.5 hours. Short tandem repeat analyses confirmed the cell origin, although loss of heterozygosity occurred. Karyotype analyses revealed a heterogeneous composition of the cell culture and the karyogram itself showed aberrations and changes in the chromosome numbers. Real-time PCR and immunocytochemical fluorescence staining revealed the expression of the stem cell markers such as ABCG2, p63, OCT4, c-MYC, and SOX2 as well as the conjunctival cytokeratin K19. CONCLUSIONS: PeCa-UkHb-01 cells fulfill the criteria of a cell line. They display characteristics of ocular carcinoma cells and therefore the presented cell line might serve for further basic research in ophthalmic oncology.

Aganirsen antisense oligonucleotide eye drops inhibit keratitis-induced corneal neovascularization and reduce need for transplantation: the I-CAN study.

OBJECTIVE: Eye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation. DESIGN: Multicenter, double-masked, randomized, placebo-controlled phase III study. PARTICIPANTS: Analysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 µg/day/eye) or placebo twice daily for 90 days and were followed up to day 180. MAIN OUTCOME MEASURES: The primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL. RESULTS: Although no significant differences in VA scores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20% (P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious TEAEs (2 with aganirsen and 1 with placebo) were considered treatment-related. CONCLUSIONS: This first phase III study on a topical inhibitor of corneal angiogenesis showed that aganirsen eye drops significantly inhibited corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well tolerated.

Consensus statement on indications for anti-angiogenic therapy in the management of corneal diseases associated with neovascularisation: outcome of an expert roundtable.

The cornea is the clear window at the front of the eye and is the eye's main refractive medium. Its transparency is essential for vision. Corneal neovascularisation is a common clinical problem with serious consequences for vision; it can compromise corneal transparency and plays a major role in corneal graft rejection by breaching corneal immune privilege. In this review, we formulate a consensus on the unmet medical needs in the management of corneal neovascularisation and outline a framework for the clinical research that is needed to identify suitable agents to meet these needs.