Clinical and Histopathological Features of Gelsolin Amyloidosis Associated with a Novel GSN Variant p.Glu580Lys.

Gelsolin amyloidosis typically presents with corneal lattice dystrophy and is most frequently associated with pathogenic GSN variant p.Asp214Asn. Here we report clinical and histopathological features of gelsolin amyloidosis associated with a novel GSN variant p.Glu580Lys. We studied DNA samples of seven members of a two-generation family. Exome sequencing was performed in the proband, and targeted Sanger sequencing in the others. The heterozygous GSN variant p.Glu580Lys was identified in six patients. The patients exhibited corneal dystrophy (5/6), loose skin (5/6) and/or heart arrhythmia (3/6) and one presented with bilateral optic neuropathy. The impact of the mutation on the protein structure was evaluated in silico. The substitution is located in the fifth domain of gelsolin protein, homologous to the second domain harboring the most common pathogenic variant p.Asp214Asn. Structural investigation revealed that the mutation might affect protein folding. Histopathological analysis showed amyloid deposits in the skin. The p.Glu580Lys is associated with corneal dystrophy, strengthening the association of the fifth domain of gelsolin protein with the typical amyloidosis phenotype. Furthermore, optic neuropathy may be related to the disease and is essential to identify before discussing corneal transplantation.

Impact of laser pulse duration on the reduction of intraocular pressure during selective laser trabeculoplasty.

PURPOSE: To evaluate the efficacy of selective laser trabeculoplasty (SLT) to lower intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG), normal tension glaucoma (NTG) or ocular hypertension (OHT), when performed with laser pulse duration of 1 ns compared with standard 3-5 ns. METHODS: Bilateral SLT with a 532 nm Q-switched neodymium-doped yttrium aluminium garnet laser was conducted in 30 patients (60 eyes) with POAG (n = 5), NTG (n = 2) or OHT (n = 23). Pulse duration was 1 ns in the right eye (30 eyes; cases) and 3-5 ns in all left eyes (controls). Main outcome measures were IOP at 1 h, 1 day, 8 weeks and 6 months, and the rate of adverse ocular tissue reactions in all eyes. RESULTS: Mean 1 ns and 3-5 ns SLT IOPs were 24.1 and 24.3 mmHg, respectively, at baseline. No statistically significant difference in mean 1 ns and 3-5 ns SLT IOP was observed at 1 h (P = 0.761), 1 day (P = 0.758), 8 weeks (P = 0.352) and 6 months postoperatively (P = 0.879). No significant difference in postoperative anterior chamber inflammation was observed between the eyes (P = 0.529). Treatment with both laser pulse durations resulted in minor ultrastructural changes in the drainage angle. CONCLUSIONS: SLT performed with a 1 ns laser pulse duration does not appear to be inferior to SLT performed with the standard 3-5 ns duration at lowering IOP in treatment-naïve patients with POAG, NTG or OHT.

Higher glucose level and systemic oxidative stress decrease the mean velocity index of the retinal artery during flickering light stimulation in type 1 diabetes.

AIM: To determine whether higher glucose level and systemic oxidative stress decrease mean velocity (MV) index of the central retinal artery (CRA) during flickering light stimulation in type 1 diabetes (T1D). METHODS: The study was performed in the period from 2008 to 2015 at the University Eye Clinic in Ljubljana. 41 patients with T1D and 37 participants without diabetes were included. MV in the CRA was measured using Doppler ultrasound diagnostics in basal conditions and during 8 Hz flickering light irritation. The plasma levels of glucose, fructosamine, 8-hydroxy-2'-deoxyguanosine (8-OHdG), triglycerides, cholesterol, and low-density lipoprotein (LDL) were measured. RESULTS: Patients with T1D had significantly higher levels of blood glucose (P<0.001), fructosamine (P<0.001), and 8-OHdG (P<0.001), but there were no significant differences in triglycerides (P=0.108), cholesterol (P=0.531), and LDL (P=0.645) between the groups. Patients with T1D also had a significantly lower MV index in the CRA (1.11±0.15 vs 1.24±0.23; P=0.010). In the T1D group, a significant negative correlation was found between the level of glucose (r=0.58; P<0.001), fructosamine (r=0.46; P=0.003), 8-OHdG (r=0.48; P=0.002) and the MV index in the CRA. At the same time, in this group fructosamine and 8-OHdG levels had a separate effect on the MV index (adjusted R2=0.38, P<0.001). CONCLUSION: Higher glucose levels, the medium-term glucose level, and systemic oxidative stress could importantly reduce retinal vasodilatation during flickering light irritation in patients with T1D.

Prognostic factors of choroidal melanoma in Slovenia, 1986-2008.

INTRODUCTION: Choroidal melanoma is the most common primary malignancy of the eye, which frequently metastasizes. The Cancer Registry of Slovenia reported the incidence of choroid melanoma from 1983 to 2009 as stable, at 7.8 cases/million for men and 7.4/million for women. The aim of the retrospective study was to determinate the prognostic factors of survival for choroidal melanoma patients in Slovenia. PATIENTS AND METHODS: From January 1986 to December 2008 we treated 288 patients with malignant choroidal melanoma; 127 patients were treated by brachytherapy with beta rays emitting ruthenium-106 applicators; 161 patients were treated by enucleation. RESULTS: Patients with tumours thickness < 7.2 mm and base diameter < 16 mm were treated by brachytherapy and had 5- and 10-year overall mortality 13% and 32%, respectively. In enucleated patients, 5- and 10-year mortality was higher, 46% and 69%, respectively, because their tumours were larger. Thirty patients treated by brachytherapy developed local recurrence. Twenty five of 127 patients treated by brachytherapy and 86 of 161 enucleated patients developed distant metastases. Patients of age ≥ 60 years had significantly lower survival in both treatment modalities. For patients treated by brachytherapy the diameter of the tumour base and treatment time were independent prognostic factors for overall survival, for patients treated by enucleation age and histological type of tumour were independent prognosticators. In first few years after either of treatments, the melanoma specific annual mortality rate increased, especially in older patients, and then slowly decreased. CONCLUSIONS: It seems that particularly younger patients with early tumours can be cured, whereby preference should be given to eyesight preserving brachytherapy over enucleation.

Optical coherence tomography for an in-vivo study of posterior-capsule-opacification types and their influence on the total-pulse energy required for Nd:YAG capsulotomy: a case series.

BACKGROUND: Posterior capsule opacification (PCO) is the most common post-operative complication associated with cataract surgery and is mostly treated with Nd:YAG laser capsulotomy. Here, we demonstrate the use of high-resolution spectral-domain optical coherence tomography (OCT) as a technique for PCO analysis. Additionally, we evaluate the influence of PCO types and the distance between the intraocular lens (IOL) and the posterior capsule (PC), i.e., the IOL/PC distance, on the total-pulse energy required for the Nd:YAG laser posterior capsulotomy. METHODS: 47 eyes with PCO scheduled for the Nd:YAG procedure were examined and divided into four categories: fibrosis, pearl, mixed type and late-postoperative capsular bag distension syndrome. Using custom-made computer software for OCT image analysis, the IOL/PC distances in two dimensions were measured. The IOL/PC distances were compared with those of a control group of 15 eyes without PCO. The influence of the different PCO types and the IOL/PC distance on the total-pulse energy required for the Nd:YAG procedure was analyzed. RESULTS: The total-pulse energy required for a laser capsulotomy differs significantly between PCO types (p = 0.005, Kruskal-Wallis test). The highest energy was required for the fibrosis PCO type, followed by mixed, pearl and late-postoperative capsular bag distension syndrome. The IOL/PC distance also significantly influenced the total-pulse energy required for laser capsulotomy (p = 0.028, linear regression). Lower total-pulse energy was expected for a larger IOL/PC distance. CONCLUSIONS: Our study indicates that the PCO types and the IOL/PC distance influence the total-pulse energy required for Nd:YAG capsulotomy. The presented OCT method has the potential to become an additional tool for PCO characterization. Our results are important for a better understanding of the photodisruptive mechanisms in Nd:YAG capsulotomy.

Localized Linear IgA Bullous Dermatosis and a Recurrent Cicatricial Ectropion of the Eyelid: A Case Report of a Sixteen-Year Follow-up.

Cicatrizing ectropion of the eyelid is an uncommon condition, possibly resulting in significant ocular morbidity. A potential cause can be a systemic disease, including autoimmune blistering disease (ABD). We herein report a case with a sixteen-year follow-up of a patient with a chronic cicatrizing unilateral ectropion caused by linear IgA bullous dermatosis (LABD). LABD is an ABD, characterized by the accumulation of IgA anti-basement membrane autoantibodies. It has a varied presentation; however, localized or ophthalmic manifestations have been infrequently described. The case demonstrates the benefits of immunohistochemistry in obtaining the correct diagnosis, and difficulties in the medical and surgical management of a recurrent cicatricial ectropion caused by chronic systemic disease.

Morphological characteristics of conjunctival squamous papillomas in relation to human papillomavirus infection.

OBJECTIVE: To determine the prevalence of a broad spectrum of human papillomavirus (HPV) types in conjunctival papillomas and a possible difference in clinical and histopathological presentation of HPV-positive and HPV-negative papillomas. METHODS: Formalin-fixed, paraffin-embedded papilloma tissue specimens obtained from 25 patients were analysed using six different PCR-based methods targeting 87 HPV types from four different papillomavirus (PV) genera: α-PV, ß-PV, γ-PV and µ-PV, and in situ hybridisation for HPV-6/HPV-11. Slides were reviewed for pedunculated or sessile growth, the presence of goblet cells, keratinising or non-keratinising epithelium, elastosis, atypia and koilocytes. RESULTS: α-PV types HPV-6 and HPV-11 were detected in 19/25 (76%) conjunctival papilloma tissue specimens, 9 (47%) of which were also HPV-6/HPV-11 positive with in situ hybridisation. Six different ß-PV types-HPV-9, HPV-12, HPV-20, HPV-21, HPV-22, HPV-24-were additionally detected in four cases, all of which were also HPV-6/HPV-11 positive. No γ-PVs or µ-PVs were found in any of the tested tissues samples. Extralimbal location (p=0.021), presence of goblet cells (p=0.005), non-keratinising squamous epithelium (p=0.005), and absence of elastosis (p=0.005) were associated with the presence of HPV-6/HPV-11. CONCLUSIONS: We demonstrated that certain clinical and histological features are more frequently associated with HPV infection and that HPV genera other than α-PV are most probably not significant factors in conjunctival papilloma occurrence.

Glaucoma progression and role of glaucoma surgery in patients with Boston keratoprosthesis.

PURPOSE: The aim of this study was to evaluate glaucoma onset and progression after implantation of Boston Keratoprostheses (B-KPro) and the role of glaucoma surgery. METHODS: Records of patients with B-KPro implantation during 2004 to 2009 were reviewed. Parameters relevant to B-KPro surgery and glaucoma status were recorded. The data were analyzed in 5 groups based on the preoperative diagnosis. RESULTS: One hundred six eyes of 87 patients were included, and the average age was 54 ± 6.7 years. Forty-six percent were female. Eighteen eyes had a B-KPro with a titanium back plate, and the others had a poly(methyl methacrylate) back plate. Thirty-three eyes were pseudophakic, and the rest were left aphakic. The follow-up time was 3.3 ± 1.0 years. Indications for implantation included past infection, congenital glaucoma, trauma, autoimmune diseases, aniridia, burns, and others. Sixty-six percent of the eyes had glaucoma preoperatively, and 26% developed de novo glaucoma afterward. The mean intraocular pressure (by finger palpation) was 16.5 ± 5.7 mm Hg. Reliable visual field tests were only available in 59% of the eyes; hence, the cup-to-disc ratio of the optic nerve head was used as the main outcome measure. In B-KPro-implanted eyes with glaucoma, 65% had undergone glaucoma surgery at some point, and 30% did not show progression. Thirty-one percent of the total cohort had disc pallor with a cup-to-disc ratio of <0.8. CONCLUSIONS: Glaucoma in B-KPro remains a challenge, despite aggressive attempts to slow down its progression. Patients with glaucoma before B-KPro implantation should be considered for glaucoma surgery before or simultaneously with B-KPro implantation. The high number of eyes with disc pallor suggests that additional mechanisms other than elevated intraocular pressure may play a role in optic neuropathy.

A novel murine model for keratoprosthesis.

PURPOSE: To establish a murine model for keratoprosthesis. METHODS: A miniature keratoprosthesis (m-KPro) device was created consisting of a poly[methyl methacrylate] front part and a titanium back plate, designed after the Boston KPro, which is in widespread clinical use. BALB/c mice were used and a 2 mm in diameter donor cornea was punched out. After 2-mm trepanation of the syngeneic recipient cornea, extracapsular crystalline lens extraction was performed. The m-KPro was assembled onto the cornea button in a similar manner to human KPro implantation. The cornea-device complex was secured to the recipient bed with eight interrupted 11-0 sutures. All mice (n = 10) were followed up for 8 weeks postoperatively. RESULTS: All m-KPros were successfully implanted and retained in all 10 animals. There were no critical complications such as endophthalmitis, corneal melting, device extrusions, leakage, extensive inflammation, or weight loss in the animals. We observed mild to moderate donor and host corneal neovascularization in all cases throughout the follow-up period. CONCLUSIONS: We have established a novel murine model of KPro implantation that we anticipate will serve as a good experimental system for evaluating host responses after KPro surgery.

Preserved scleral patch graft for unexpected extreme scleral thinning found at the scleral buckling procedure: a case report.

Pre-existing scleral pathology is an important risk factor for globe rupture during scleral buckling procedures. We report here, the surgical management of an unexpected scleral pathology found at the scleral buckling procedure in a retinal detachment patient. A 77-year-old white female with retinal detachment underwent a scleral buckling procedure. The surgery was converted into a scleral graft procedure, as extreme scleral thinning was found intraoperatively. An alcohol-preserved donor sclera graft was used. The second surgery for definitive retinal alignment was performed two weeks later. The presented case of an unexpected scleral pathology in a retinal detachment patient was managed with a combination of scleral grafting and pars plana vitrectomy, without any major complications. The anatomical outcome was excellent and the scleral rupture was prevented; the visual outcome was satisfactory. A conversion of the scleral buckling procedure into a scleral graft procedure has proved to be safe and effective for unexpected scleral pathology.

Transcanalicular diode laser-assisted dacryocystorhinostomy.

OBJECTIVE: We present a prospective, non-comparative case series study of 126 consecutive diode laser-assisted transcanalicular dacryocystorhinostomy (TCL-DCR) procedures on 122 patients. We analyzed success rate, procedure time and amount of laser energy needed for a 5 mm osteotomy. MATERIALS AND METHODS: One hundred and twenty-two patients with nasolacrimal duct obstruction were included in the study. The procedure was performed under general anesthesia, and the nasal mucosa was anesthetized. An endoscope was used for examination of the lacrimal pathways. The site of osteotomy was determined with transillumination of the lateral nasal wall. We achieved osteotomy by applying laser energy via an optic fiber. We used a 980 nm diode laser with power of 10 Watts. We inserted a bicanalicular silicone stent as the last step. Success of procedure was absence of epiphora (subjective), or patency of the lacrimal drainage system on irrigation (objective). RESULTS: We performed 126 successive endoscopic laser (EL-DCR) with bicanalicular intubation in 122 patients. The average procedure time was 12 min, and on average 245 Joules of laser energy was needed. The silicone stents were removed three to eight months after surgery. We observed absence of epiphora and a patent nasolacrimal duct on irrigation in 105 out of 126 treated eyes. Eighteen patients had epiphora despite a patent nasolacrimal duct on irrigation. This yields a success rate of 83.3%, with an average follow-up period of 12 months. CONCLUSIONS: The 980 nm EL-DCR with bicanalicular intubation is a new contribution to the field of lacrimal surgery. It is a minimally invasive quick procedure yielding a high success rate.

Trauma of the lacrimal drainage system: retrospective study of 32 patients.

AIM: To assess retrospectively the results and complications of surgical techniques applied in the treatment of patients with trauma of the lacrimal drainage system. METHODS: Out of 32 patients with lacrimal drainage system trauma included in the study, 25 were treated at the University Eye Clinic, Ljubljana Medical Center, Ljubljana, Slovenia, from 1999 to 2003, and 7 were referred for secondary repair from other health care institutions in the same time period. All patients with fresh injuries underwent surgery within 48 h. The patients were followed up to a year after surgery. We evaluated the function of the lacrimal drainage system by irrigation at the last follow-up visit. RESULTS: Patent lacrimal drainage system was achieved in all 25 patients with primary reconstruction of the injury. Restenosis of the canaliculus occurred in 4 out of 7 patients after secondary reconstruction. CONCLUSIONS: Early repair of the lacrimal drainage system eliminates complications in comparison with secondary repair. Repair of the lacrimal drainage system may be delayed for up to 48 h, if an experienced operating team is available.

Repetitive Er:YAG laser irradiation of human skin: a histological evaluation.

BACKGROUND AND OBJECTIVE: Deep coagulation of skin collagen by Er:YAG laser repetitive pulses has been predicted by previous theoretical models and later demonstrated on animal skin. The goal of this study was to determine the effect of repetitive Er:YAG laser pulses on human skin and its response to this treatment. STUDY DESIGN/MATERIALS AND METHODS: Lid skin of six female volunteers with blepharochalasis has been treated with laser at day 0, 7, and 21 before elective surgery-blepharoplasty. The treated skin was excised as part of the procedure and prepared for further histological examination. We used a 2,940 nm Er:YAG laser (Fidelis M320A by Fotona) with 'smooth' mode parameters: fluence from 0.50 to 2.00 J/cm2; six pulses per packet; 550 microsecond/pulse, 250 millisecond/packet; single pass, no overlapping; spot size 5 mm; repetition rate 20 Hz. RESULTS: We observed deep collagen denaturation at laser fluences of 1.25 J/cm2 and over; epidermal damage was proportional to fluence with total coagulation of the epidermal layer at fluences of 1.75 J/cm2 and over. At day 7 after laser treatment we observed a complete regeneration of the epidermal layer and a regeneration zone within the dermis with prominent infiltration of CD68+ monocytes/macrophages. At day 21 after laser treatment we observed collagen remodeling and (myo-)fibroblast proliferation at tissue depths of up to 240 microm. CONCLUSIONS: Repetitive Er:YAG laser irradiation is effective in deep denaturation and remodeling of human skin collagen in vivo, with less epidermal damage compared to standard Er:YAG laser skin resurfacing.

Acute ultrastructural changes of the trabecular meshwork after selective laser trabeculoplasty and low power argon laser trabeculoplasty.

BACKGROUND AND OBJECTIVES: To compare the histopathological changes in the human trabecular meshwork after low power argon laser trabeculoplasty (ALT) and selective laser trabeculoplasty (SLT) with a Q-switched, frequency-doubled, neodymium:yttrium-aluminium-garnet (Nd:YAG) laser. STUDY DESIGN/MATERIALS AND METHODS: In gonioscopically normal trabecular meshwork of three patients awaiting enucleation due to malignant melanoma of the choroid, SLT and ALT were performed 1-5 days prior to enucleation. In each eye, the lower half of trabecular meshwork received SLT, one quadrant low power (460 mW) ALT and one quadrant was left untreated. Specimens were evaluated with light and transmission electron microscopy. RESULTS: A sharp demarcation line was visible between the laser treated and untreated intact trabecular meshwork after ALT and SLT. Both lasers caused disruption of trabecular beams, but the extent of the damage was smaller after SLT. The collagen component of trabecular beams was mostly amorphous, the long-spacing collagen was scanty after ALT, but more abundant after SLT. In the intertrabecular spaces fragmented cells and tissue debris with only a few pigmented cells were observed. Some endothelial cells were desquamated, but appeared slightly better preserved after SLT than ALT. CONCLUSIONS: Our ultrastructural comparison of the morphological changes after low power ALT and SLT in patients demonstrated that both lasers caused splitting and fragmentation of the trabecular beams of the trabecular meshwork, but the extent of the damage was smaller and the preservation of long-spacing collagen better after SLT than after ALT.

Prognostic factors in open eye injury managed with vitrectomy: retrospective study.

AIM: To evaluate surgery results and establish prognostic factors that predicted final functional (good or poor vision) and anatomic (final retinal detachment) outcome in open eye injury involving the posterior segment managed with pars plana vitrectomy. METHODS: Medical records of 52 consecutive patients with open eye injury involving the posterior segment were retrospectively reviewed. Specific variables of a system for classifying mechanical injuries of the eye were analyzed: the type of injury (defined by the mechanism of injury), grade of injury (defined by initial visual acuity), zone of injury (defined by the location of the wound), and relative afferent pupillary defect. Additional variables, such as wound length, retinal detachment, endophthalmitis, and timing of vitrectomy, were also included in the analysis. Final visual outcome and retinal attachment rate were recorded. Data were analyzed with chi-square test, univariate analysis for predictors, and multivariate logistic regression analysis. RESULTS: After a mean follow up of 20.0+/-10.5 months, 50% of eyes achieved visual acuity 0.5 or better, 27% of eyes achieved visual acuity 0.1 or worse, and 10% of eyes had final retinal detachment. According to univariate analysis results, the following parameters were predictors of good vision (visual acuity > or =0.5 in comparison with visual acuity <0.5): grade of injury (p=0.008), zone of injury (p=0.01), afferent pupillary response (p<0.001), wound length (p=0.002), and initial retinal detachment (p=0.009). The predictors of poor vision (visual acuity < or =0.1 in comparison with visual acuity >0.1) were zone of injury (p<0.001), relative afferent pupillary defect (p<0.001), wound length (p=0.002), and initial retinal detachment (p<0.001). Relative afferent pupillary defect (p=0.003) and initial retinal detachment (p<0.001) were predictors of final retinal detachment with proliferative vitreoretinopathy. However, multivariate logistic regression analyses revealed that relative afferent pupillary defect was the only significant factor for poor visual acuity (odds ratio, 10.3; 95% confidence interval, 1.1-92; p=0.04). On the other hand, none of the variables was a significant independent predictor for either good visual acuity or final retinal detachment. CONCLUSION: Half of the eyes with a good final visual outcome in our study were successfully managed with pars plana vitrectomy for open eye injury after trauma. The classification system may become useful prognostic tool for visual outcome in posterior segment ocular injuries managed with vitrectomy. Relative afferent pupillary defect as a functional test is a good predictor for visual outcome.