Sigrid Roters

A homozygous RAB3GAP2 mutation causes Warburg Micro syndrome

Warburg Micro syndrome and Martsolf syndrome are clinically overlapping autosomal recessive conditions characterized by congenital cataracts, microphthalmia, postnatal microcephaly, and developmental delay. The neurodevelopmental and ophthalmological phenotype is more severe in Warburg Micro syndrome in which cerebral malformations and severe motor and mental retardation are common. While biallelic loss-of-function mutations in RAB3GAP1 are present in the majority of patients with Warburg Micro syndrome; a hypomorphic homozygous splicing mutation of RAB3GAP2 has been reported in a single family with Martsolf syndrome. Here, we report a novel homozygous RAB3GAP2 small in-frame deletion, c.499_507delTTCTACACT (p.Phe167_Thr169del) that causes Warburg Micro syndrome in a girl from a consanguineous Turkish family presenting with congenital cataracts, microphthalmia, absent visually evoked potentials, microcephaly, polymicrogyria, hypoplasia of the corpus callosum, and severe developmental delay. No RAB3GAP2 mutations were detected in ten additional unrelated patients with RAB3GAP1-negative Warburg Micro syndrome, consistent with further genetic heterogeneity. In conclusion, we provide evidence that RAB3GAP2 mutations are not specific to Martsolf syndrome. Rather, our findings suggest that loss-of-function mutations of RAB3GAP1 as well as functionally severe RAB3GAP2 mutations cause Warburg Micro syndrome while hypomorphic RAB3GAP2 mutations can result in the milder Martsolf phenotype. Thus, a phenotypic severity gradient may exist in the RAB3GAP-associated disease continuum (the “Warburg–Martsolf syndrome”) which is presumably determined by the mutant gene and the nature of the mutation.

Ultrasound biomicroscopy and its value in predicting the long term outcome of viscocanalostomy.

Aims: To examine whether the early postoperative morphology at the site of sclerectomy, as visualised by ultrasound biomicroscopy (UBM), is an indicator of the mechanisms that lower intraocular pressure (IOP) and/or predictors of the long term outcome of viscocanalostomy. Methods: 15 eyes of 14 patients with medically uncontrolled open angle glaucoma and no history of surgery underwent viscocanalostomy according to Stegmann’s technique. Ultrasound biomicroscopy was performed during the first month after surgery. The following parameters were assessed: dimensions of the intrascleral “lake,” presence of a filtering bleb, presence of a subconjunctival cavity or a suprachoroidal hypoechoic area, and the thickness of the residual trabeculocorneal membrane. A complete ophthalmological examination was performed the day before and the day after surgery. Follow up visits were scheduled 1 week, 4 weeks, 6 months, and 12 months after surgery. Results: At 1 year successful control of IOP (<20 mm Hg) was achieved without further manipulation or medication in six of 15 eyes. The size of the intrascleral “lake” (average 0.62 mm3) did not correlate with later IOP; however, a visible route under the scleral flap and accidental perforation of the trabeculocorneal membrane were associated with long term lowering of IOP. Normal thickness of the trabeculocorneal membrane (0.10–0.15 mm) was indicative of IOP control with and without medication. When UBM showed an early collapse of the intrascleral cavity, control of IOP was not achieved. Other UBM findings did not predict long term function. Conclusion: In accordance with previous studies, the authors found that UBM examination is a useful method to evaluate outflow mechanisms after glaucoma surgery. This study shows that UBM imaging of external filtration during the early postoperative period can be used to predict the success of viscocanalostomy. However, to establish conclusively what parameters of UBM predict successful viscocanalostomy a larger number of patients must be studied.

Sutureless amniotic membrane fixation using fibrin glue for ocular surface reconstruction in a rabbit model.

Purpose: Amniotic membrane transplantation has become an important treatment option for corneal surface reconstruction. However, suture fixation of the transplant has various disadvantages like corneal irritation, scarring, graft loss due to membrane shrinkage, and the need for subsequent suture removal. Replacement of sutures by bioadhesives might be an advantageous alternative. This controlled study was designed to evaluate a new sutureless technique for amniotic membrane fixation onto the corneal surface by using fibrin glue. Methods: Standardized disks of cryopreserved amniotic membranes were transplanted onto the deepithelialized cornea of 12 rabbits using either conventional suture fixation or a new fibrin glue technique. The rabbits were followed-up with slit-lamp examination and fluorescein staining until epithelialization was completed. Consecutively, the rabbits were killed and the eyes processed for histology and immunohistochemistry for cytokeratin-3. Results: All membranes of both groups stayed in place throughout the follow-up time and showed a progressive graft epithelialization that was completed after 12 days. Whereas suture-fixated membranes showed progressive tissue shrinkage, fibrin-glued sheets remained unaltered. In the bioadhesive group, histology revealed a smooth fibrin layer in the graft-host interface and a continuous, stratified layer of cytokeratin-3 expressing corneal epithelial cells on the membrane surface. In contrast, suture-fixated membranes showed contracted and prominent membrane edges with epithelial ingrowth into the submembrane interface. Conclusion: Our results demonstrate the general feasibility of reproducible and reliable sutureless amniotic membrane fixation onto the corneal surface in rabbits. Stable adherence is maintained until epithelialization is completed. The sutureless technique gives sufficient manipulation time for the sheet before the final cross-linking process is completed. Furthermore, several advantageous characteristics could be demonstrated as increased biocompatibility, better epithelialization pattern and the lack of membrane shrinkage.

Bullous keratopathy as a complication of trabeculectomy with mitomycin C

BackgroundThe routine use of mitomycin C to enhance glaucomatous filtering surgery has found wide acceptance. Complications of the application of mitomycin C have been repeatedly noticed. We now report a previously undescribed complication showing a toxic effect of mitomycin C to the corneal endothelium.MethodsPatients underwent routine trabeculectomy with mitomycin C. Following surgery, the eyes were examined by biomicroscopy and specular microscopy of the corneal endothelium.ResultsIn two cases, we observed a partial decompensation of the corneal endothelium resulting in a well-demarcated clear zone of the cornea and a second zone with thickening of the cornea and a bullous keratopathy adjacent to the filtering bleb. The specular microscopy showed marked irregularities of the endothelial cells and areas of necrosis in those parts of the cornea close to the filtering bleb.ConclusionsThe two cases described here demonstrate that if the corneal endothelium is already compromised before surgery, the application of mitomycin C may have an additional toxic effect on the endothelium and may result in a partial bullous keratopathy. Surgeons should be aware of this complication.

The effect of latanoprost 0.005% once daily versus 0.0015% twice daily on intraocular pressure and aqueous humour protein concentration in glaucoma patients. A randomized, double-masked comparison with timolol 0.5%

Abstract• Background: Latanoprost is a PGF2α analogue which reduces the intraocular pressure (IOP) by increasing the uveoscleral outflow. The objective of this study was to investigate the effect of two different regimens of latanoprost on the diurnal IOP and also the effect of latanoprost on the blood-aqueous barrier measured with a laser flare cell meter (Kowa FM-500). Moreover, the safety aspects of the two regimens regarding hyperemia were studied. • Methods: A double-masked, randomized study was performed in 30 patients (9 males, 21 females; mean age 61.9 years) with primary open-angle glaucoma or pseudoexfoliation glaucoma. Twenty patients were treated with latanoprost 0.0015% twice daily or 0.005% once daily for 3 weeks in a cross-over design. Ten patients received timolol 0.5% twice daily as control. • Results: Latanoprost 0.005% once daily reduced IOP (± SEM) more effectively than latanoprost 0.0015% twice daily (9.8±0.9 mm Hg and 6.7±0.9 mm Hg, respectively). There was a statistically significant increase in the aqueous humour protein concentration within the timolol group (P=0.004), but not within the latanoprost group (P=0.97). There was no statistically significant difference in the change in aqueous humour protein concentration from baseline between latanoprost and timolol groups (P=0.08). No statistically significant difference in conjunctival hyperemia between the two latanoprost regimens was found (P=0.37). • Conclusion: Latanoprost 0.005% once daily reduced IOP more effectively than latanoprost 0.0015% twice daily (P<0.001). Latanoprost had no statistically or clinically significant effect on the blood-aqueous barrier. There was no difference in hyperemia between the two regimens. Both concentrations of latanoprost reduced IOP at least as well as timolol 0.5% eye drops.

Outcome of combined penetrating keratoplasty with vitreoretinal surgery for management of severe ocular injuries

Purpose To assess the effectiveness of a combined procedure (pars plana vitrectomy with temporary keratoprosthesis, vitreoretinal surgery, and penetrating keratoplasty) and to determine which factors influence corneal transplant success rates. Methods Records for 34 severely injured eyes of 31 consecutive patients who underwent penetrating keratoplasty in combination with vitreoretinal surgery between 1991 and 1998, with a follow-up of at least 12 months, were evaluated retrospectively. Analysis was focused on ocular history, functional and anatomic anterior and posterior segment outcome, and complications. Results Penetrating keratoplasty was performed in 10 eyes (29%) within 8 weeks of trauma and in 24 eyes (71%) as a secondary procedure. Initial improvement in visual acuity (VA) was achieved in 47% of eyes; at the end of the follow-up, 74% of the eyes had attained equal or better VA than the initial postsurgical VA. Reasons for poor final VA were hypotony or phthisis (35%) and recurrent retinal detachment (11%). Corneal grafts remained clear for 1 year in 65% of eyes. Transplant failure was less in eyes that did not need a permanent silicone oil tamponade, when the retina was attached before surgery, and in eyes that were grafted later after trauma and received no further surgery. These were some conditions that were associated with a longer mean graft survival time, but without statistical significance. There was no difference in eyes according to the trauma mechanism, preoperative intraocular pressure, or graft size. Conclusions Penetrating keratoplasty in severely injured eyes is often complicated by ciliary body malfunction and secondary transplant failure. Although the functional outcome of a combined procedure is limited by primary and secondary tissue destruction, preserving ambulatory vision is possible and thus improves the quality of life, at least in patients with single remaining eyes.

Ultrasound Biomicroscopy In Chronic Ocular Hypotony: Its Impact on Diagnosis and Management

Purpose To determine the value of ultrasound biomicroscopy (UBM) in the assessment of ocular hypotony in cases where the underlying pathologic mechanism remains unclear after extensive clinical examination. Methods In a retrospective study, the records of 60 patients who had undergone UBM to elucidate the underlying structural abnormalities of chronic ocular hypotony (intraocular pressure of 0–8 mmHg) were evaluated. Most patients (47 of 60 eyes) had a history of intraocular surgery or of other ocular diseases (e.g., uveitis), and after careful clinical examination, the cause had remained unclear. All patients were observed up for a minimum of 12 months. Results The associated pathoanatomy of the hypotony was demonstrated by UBM in 95% of the cases. Ciliary body abnormalities were present in 80% of the eyes. Therapeutic intervention was associated with restoration of normal ocular pressure in 50% of the cases. Often more than one intervention was necessary. A long duration of hypotony did not impede reaching the therapeutic goal of normalizing intraocular pressure and preventing phthisis. Conclusions Ultrasound biomicroscopy is a new tool for detecting the underlying structural abnormalities in ocular hypotony. In cases where clinical examination is not sufficient it can be of great help in deciding on a course of treatment.

Signal quality of biometry in silicone oil–filled eyes using partial coherence laser interferometry

Purpose: To assess the practical feasibility and signal quality of axial length measurements by partial coherence laser interferometry in silicone oil–filled eyes with previous complicated vitreoretinal surgery. Settings: Department of Ophthalmology, University Cologne, Cologne, Germany. Methods: Using a Zeiss IOLMaster, axial length measurements and signal‐to‐noise ratios of optical biometry in silicone oil–filled eyes (n = 45) and contralateral eyes without tamponade (n = 41) were analyzed. Results: Axial length measurements with signal‐to‐noise ratio ≥2 were feasible in 41 of 45 silicone oil–filled eyes (91%) and 37 of 41 eyes without tamponade (90%). Cataract, central retinal detachment, vitreous hemorrhage, and emulsified oil droplets attached to the intraocular lens were reasons for failure of partial coherence laser interferometry. The signal‐to‐noise ratio of the first 2 measurements was significantly smaller (P = .04) in silicone‐filled eyes (4.4 ± 2.0) than in eyes without tamponade (5.5 ± 3.0). Axial lengths of the oil–filled eye and the contralateral eye showed a significant intraindividual correlation (P<.0001, Spearman r = 0.84). Conclusions: Partial coherence laser interferometry shows good clinical practicability in silicone oil–filled eyes with previous complicated vitreoretinal surgery. Further studies are needed to assess the reliability of these measurements with regard to postoperative refraction after combined oil removal and cataract surgery.

Primary silicone oil tamponade in the management of severe intraocular foreign body injuries: an 8-year follow-up.

Purpose: To evaluate the long-term outcome of pars plana vitrectomy and primary silicone oil tamponade in patients with severe intraocular foreign body (IOFB) injuries and high risk of proliferative vitreoretinopathy (PVR). Methods: This retrospective consecutive study included 23 patients with severe IOFB injuries who had extensive lacerations including sclera, choroid, and retina, and were complicated by predictive factors for elevated proliferative activity and an unfavorable outcome. All patients underwent pars plana vitrectomy, removal of the IOFB, and primary silicone oil tamponade and were followed up for a mean 8.9 years. Main functional outcome was assessed as final best-corrected visual acuity. Anatomic success was defined as permanent retinal attachment. Results: PVR occurred in 70% of all eyes and required 16 revisions. Silicone oil was removed in 78% of the eyes after a mean tamponade duration of 9.1 months. Complete retinal attachment was achieved in 83% of the eyes. Three eyes developed a persisting hypotony that was stabilized under permanent silicone oil. Functional stabilization was observed in the third year resulting in a final visual acuity of 20/630. Useful vision of better than 20/400 could be preserved in 55% of the patients. Only one eye underwent a late enucleation after 6.8 years. Conclusions: Primary silicone oil stabilizes the retina during the critical period of active PVR and may limit the visual loss in selected high-risk eyes in the long term.

Combined penetrating keratoplasty and vitreoretinal surgery with silicone oil: a 1-year follow-up

Abstract Background. The aim of this study was to assess the functional outcome of eyes with corneal and vitreoretinal diseases following combined surgical procedures (pars plana vitrectomy with temporary keratoprosthesis, vitreoretinal surgery, and penetrating keratoplasty with intravitreal silicone oil tamponade) and to evaluate the factors preserving the clarity of grafts. Methods. Fifty-three eyes from 49 consecutive patients, operated on between 1991 and 1998 and followed up for at least 12 months, were evaluated retrospectively. The evaluation focused on ocular history, visual acuity (VA), intraocular pressure, anterior and posterior anatomical outcome, and complications. Results. The average follow-up was 28.4 months±18.8 months (range 12–84 months); at the final visit 58% of the eyes had better VA, and 73% had equal or better acuity ; the cornea remained clear in 68% of the eyes. A decrease in VA was caused by: loss of light perception in 2 eyes, one of which had to be enucleated because of painful phthisis; hypotony or phthisis in 23 eyes; recurrent retinal detachment in 4 eyes that were operated because of trauma; and immunological reaction in 2 eyes. Preoperative factors that contributed to a clear graft, but were not significant, were: lack of trauma (74%), no actual silicone oil filling (78%), preoperative VA of hand movement or better (79%), and attached retina (73%). Further surgery was needed in 55% of cases. The risk of transplant failure was significantly lower in eyes that did not undergo additional surgery (p=0.0001). Conclusion. The long-term results of combined surgery with penetrating keratoplasty in eyes that would otherwise be untreatable is often limited by anterior segment complications, mainly secondary graft failure and ciliary body malfunction. For optimal preservation of graft clarity, stable ocular status should be achieved before transplantation to minimize the necessity for further surgery.