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.

UBM examination demonstrated several aqueous humour drainage pathways. A low-reflective diffuse subconjunctival space meant persistent filtration in all eyes. More than 1 year after surgery 92.8% of eyes had a remaining intrascleral cavity. In almost half of the patients an additional suprachoroidal outflow was observed, significantly correlated with a lower IOP.

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.

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 mm 3 ) 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. Several investigators have shown renewed interest in surgical reduction of intraocular pressure (IOP) by nonperforating glaucoma surgery. Non-perforating glaucoma surgery avoids opening the anterior chamber and decompressing the eye, thus circumventing many serious complications associated with standard trabeculectomy.1 In open angle glaucoma, the endothelium of Schlemm's canal and the immediately adjacent trabecular meshwork show increased resistance to aqueous outflow, 2 resulting in increased IOP. Recently, a new technique of non-penetrating glaucoma surgery, viscocanalostomy, has been described; it results in better outflow in open angle glaucoma.3 4 In this procedure Schlemm's canal is unroofed and Descemet's membrane is separated 1-2 mm from the corneoscleral junction, resulting in a thinner but intact window to the anterior chamber, through which aqueous humour diffuses into a subscleral lake created by the removal of an inner scleral flap. Filtration is improved when the diameter of Schlemm's ...

This novel surgical approach and the placement of the silicone tube described here have several advantages. Its intrascleral course minimizes the risk of conjunctival erosion and associated infections. No cyclodialysis is performed. Connection to the suprachoroidal space exploits the resorptive capability of the choroid. It guarantees drainage but also provides a natural counterpressure, avoiding severe postoperative hypotony. The suprachoroidal shunt presented here achieves good follow-up results in terms of IOP control. No serious complications have been observed. This new method promises to be an effective surgical technique and presents a new therapeutic option in intractable glaucoma. Fibroblast reaction obstructing the posterior lumen, seemed to be the only factor limiting drainage. Further studies and experiments will be needed to elucidate the exact physiologic mechanisms underlying the draining, the capacity and duration of the draining effect, and the histologic background of suprachoroidal scarring.