Molecular mechanism of CHRDL1-mediated X-linked megalocornea in humans and in Xenopus model.

Chordin-Like 1 (CHRDL1) mutations cause non-syndromic X-linked megalocornea (XMC) characterized by enlarged anterior eye segments. Mosaic corneal degeneration, presenile cataract and secondary glaucoma are associated with XMC. Beside that CHRDL1 encodes Ventroptin, a secreted bone morphogenetic protein (BMP) antagonist, the molecular mechanism of XMC is not well understood yet. In a family with broad phenotypic variability of XMC, we identified the novel CHRDL1 frameshift mutation c.807_808delTC [p.H270Wfs*22] presumably causing CHRDL1 loss of function. Using Xenopus laevis as model organism, we demonstrate that chrdl1 is specifically expressed in the ocular tissue at late developmental stages. The chrdl1 knockdown directly resembles the human XMC phenotype and confirms CHRDL1 deficiency to cause XMC. Interestingly, secondary to this bmp4 is down-regulated in the Xenopus eyes. Moreover, phospho-SMAD1/5 is altered and BMP receptor 1A is reduced in a XMC patient. Together, we classify these observations as negative-feedback regulation due to the deficient BMP antagonism in XMC. As CHRDL1 is preferentially expressed in the limbal stem cell niche of adult human cornea, we assume that CHRDL1 plays a key role in cornea homeostasis. In conclusion, we provide novel insights into the molecular mechanism of XMC as well as into the specific role of CHRDL1 during cornea organogenesis, among others by the establishment of the first XMC in vivo model. We show that unravelling monogenic cornea disorders like XMC-with presumably disturbed cornea growth and differentiation-contribute to the identification of potential limbal stem cell niche factors that are promising targets for regenerative therapies of corneal injuries.

Combined clear cornea phacoemulsification in the treatment of pseudoexfoliative glaucoma associated with cataract: significance of trabecular aspiration and ab interno trabeculectomy.

BACKGROUND: In the present study, the effectiveness of combined cataract surgery and ab interno trabeculectomy (Trabectome) in exfoliation glaucoma (PEX) was compared with combined cataract surgery and trabecular aspiration. METHODS: In this retrospective comparative cohort outcome study, 27 consecutive patients (mean age 73.41 years ± 10.78) in group 1 suffering from visually significant cataract and PEX glaucoma (mean preoperative IOP 23.41 mmHg ± 5.86) were treated with phacoemulsification combined with Trabectome; and 28 consecutive patients (73.83 years ± 8.94) were treated with phacoemulsification combined with trabecular aspiration (mean preoperative IOP 22.22 mmHg ± 6.33). The intraocular pressure (IOP) and the number of antiglaucoma eyedrops before and after surgery were evaluated. RESULTS: Examinations were performed prior to surgery, 1 day, 6 weeks, 3 months, 6 months, and 1 year after surgery. In both groups there was a statistically significant decrease in postoperative IOP during the whole follow-up period. Comparing the two groups, there was a statistically significant lower IOP in the Trabectome group 1 day (p = 0.019), 6 months (p = 0.025), and 1 year (p = 0.019) after surgery. Between the two groups, there was no statistically significant difference in the number of antiglaucoma eyedrops at any time. CONCLUSIONS: Both procedures have the ability to significantly lower the postoperative IOP during the first year. However, clear cornea phacoemulsification combined with Trabectome seems to be more effective in IOP reduction in cases of PEX glaucoma associated with cataract.

Intraocular antibody synthesis against rubella virus and other microorganisms in Fuchs' heterochromic cyclitis.

INTRODUCTION: Fuchs' heterochromic cyclitis (FHC) is a common intraocular disease of uncertain etiology that has recently been related to rubella virus (RV) infection. METHODS: We investigated the synthesis of RV-specific IgG using aqueous humor and serum samples from 63 consecutive patients with FHC. In addition, intraocular immunoglobulin G production against herpes simplex virus (HSV), varicella zoster virus (VZV), cytomegalovirus (CMV) and toxoplasma gondii was determined. In 20 patients, the detection of RV RNA was additionally performed by RT-PCR on the E1 gene. Forty-six patients with HSV- and VZV-associated uveitis, HLA B-27 positive anterior uveitis, and Posner-Schlossman syndrome served as controls. RESULTS: Specific intraocular antibody synthesis against RV was confirmed in all 63 FHC patients, whereas none of the 46 controls was positive for RV IgG. Interestingly, in 11 patients with positive RV IgG synthesis, additional HSV (eight), VZV (one) and CMV (two) specific antibodies could be detected. Only twice was viral RNA detectable by PCR in a patient with FHC. CONCLUSIONS: In this largest reported series of FHC patients, we detected a strong association between FHC and intraocular antibody synthesis against rubella virus. Furthermore, in 11 patients, it was possible to confirm an additional intraocular antibody synthesis, in particular HSV. PCR-positive results in the aqueous humor were exclusively obtained for RV. In contrast to other studies, the RV genome could only be identified in two patients (10%).

Biometric and structural ocular manifestations of Marfan syndrome.

BACKGROUND: To study biometric and structural ocular manifestations of Marfan syndrome (MFS). METHODS: Observational, retrospective, comparative cohort study in a tertiary referral center on 285 MFS patients and 267 controls. Structural and biometric ocular characteristic were compared. RESULTS: MFS eyes were longer (axial length 24.25 ± 1.74 mm versus 23.89 ± 1.31 mm, p < 0.001) and had a flatter cornea than control eyes (mean keratometry 41.78 ± 1.80 diopters (D) versus 43.05 ± 1.51 D, p < 0.001). Corneal astigmatism was greater and the central cornea was thinner in MFS eyes (530.14 ± 41.31 µm versus 547.02 ± 39.18 µm, p < 0.001). MFS eyes were more myopic than control eyes (spherical equivalent -2.16 ± 3.75 D versus -1.17 ± 2.58 D, p < 0.001). Visual acuity was reduced (0.13 ± 0.25 logMAR versus 0.05 ± 0.18 logMAR, p < 0.001) and intraocular pressure was lower in MFS eyes (14.6 ± 3.4 mmHg versus 15.1 ± 3.2 mmHg, p = 0.01). Iris transillumination defects (ITD) were significantly more common in MFS eyes (odds ratio for MFS in the presence of ITD, 3.7). Ectopia lentis (EL) was only present in MFS eyes (33.4%). History of retinal detachment was significantly more common in MFS eyes. Glaucoma was equally common in both groups. CONCLUSIONS: ITD and EL are most characteristic findings in MFS. ITD and corneal curvature should be studied as diagnostic criteria for MFS. Visual acuity is reduced in MFS. MFS patients need regular eye exams to identify serious ocular complications.

Thermography: a new option to monitor filtering bleb function?

PURPOSE: To evaluate the filtering bleb function after trabeculectomy using a new ocular surface thermography device. METHODS: Thirty-five eyes of 35 patients after trabeculectomy were included in this prospective study. The filtering bleb function was tested with a new ocular surface-oriented, infrared radiation thermographic device in a noncontact manner (TG 1000). The eyes were classified into poorly controlled and well-controlled intraocular pressure (IOP) groups according to the patients' postoperative IOP. According to Kawasaki and colleagues, the mean temperature decrease in the filtering bleb (TDB) for evaluating bleb function was used, where TDB=(mean temperature of the temporal and nasal bulbar conjunctiva)-(mean temperature of the filtering bleb). Furthermore, the filtering bleb was evaluated during 10 seconds of eye opening and a new parameter was introduced, the TB10sec. TDB and TB10sec were analyzed statistically. RESULTS: The TDB was 0.911°C (±0.467) and the TB10sec was -1.027°C (±0.312) in the well-controlled IOP group. The TDB was 0.599°C (±0.499), and the TB10sec was -0.623°C (±0.265) in the poorly controlled IOP group, respectively. The difference in TDB (P=0.045), as well as that of TB10sec (P<0.001), between the well-controlled and poorly controlled IOP groups was significant. CONCLUSIONS: Temperature decrease in the filtering bleb provides information about its function. Because of the easy handling and reproducible measurements, thermography using Tomey TG 1000 may be a useful tool in the evaluation of filtering bleb function.

Refractive lensectomy and accommodating lens implantation in a case of hyperopia.

We present a 39-year-old woman with high hyperopia who developed an intolerance to contact lenses due to dry-eye syndrome and Grave's disease. Refractive lensectomy with implantation of a custom-made +31.00 diopter (D) accommodating intraocular lens (IOL) (1CU, HumanOptics) was performed in both eyes. This foldable IOL has modified haptics with transmission elements that allow axial movement of the IOL optic and capsular bag secondary to contraction of the ciliary muscle. The calculated pseudophakic accommodation induced by the anterior shift of a +31.00 D IOL is 2.20 D per millimeter of axial displacement. After 6 months, the accommodative range determined by defocusing was 3.00 D. The subjective near point with best distance correction was 32.00 cm. Refractive lensectomy and implantation of an accommodating IOL based on focus shift may be a refractive solution in eyes with high hyperopia and a short axial length.

Adverse effects and short-term results after selective laser trabeculoplasty.

PURPOSE: To evaluate the risk of adverse effects and to demonstrate short-term results after selective laser trabeculoplasty (SLT) in glaucoma patients. METHODS: Sixty-four eyes of 64 patients with primary open-angle glaucoma, not sufficiently treated with local antiglaucomatous therapy, were included in this prospective study. Intraocular pressure (IOP), anterior chamber cells, anterior chamber flare, and vitreous haze (according to the Standardization of Uveitis Nomenclature Working Group) were examined before SLT, for 24 hours, 14 days, 6 weeks, and 3 months after laser. Furthermore, macular thickness measurements in 9 Early Treatment Diabetic Retinopathy Study subfields, including central subfield, measured by Spectralis OCT were performed. The differences between prelaser and postlaser values were obtained. RESULTS: The average of mean preoperative IOP measurement was 19.1±3.972 mm Hg compared with 12.9±2.513 (P<0.001), 13.2±3.331 (P<0.001), 14.1±2.731 (P<0.001), and 13.9±2.922 mm Hg (P<0.001) 24 hours, 14 days, 6 weeks, and 3 months post-SLT, respectively. The central subfield preoperatively was 278.14±74.355 µm compared with 277.14±71.461 (P=0.177), 277.14±71.461 (P=0.354), 287.34±74.363 (P=0.414), and 257.45±68.431 µm (P=0.214) 24 hours, 14 days, 6 weeks, and 3 months after treatment. Anterior chamber cells, anterior chamber flare, and vitreous haze were not denoted at any time of examination. CONCLUSIONS: In this study, no significant increase in macular thickness and no other adverse effects were present. Furthermore, SLT was found to significantly lower IOP in glaucoma patients in addition to local therapy. In conclusion, SLT has a good ability to reduce IOP with a minor risk of adverse effects.

Influence of prostaglandin analogue on outcome after combined cataract surgery and trabecular aspiration in pseudoexfoliative glaucoma.

PURPOSE: The aim of this study was to analyze the postoperative outcome and risk profile after combined clear cornea phacoemulsification and trabecular aspiration in the treatment of pseudoexfoliative glaucoma (PEX) associated with cataract. 
 METHODS: In this retrospective study, 69 eyes of 60 patients with visually significant cataract and PEX were treated with small-incision cataract surgery combined with trabecular aspiration. The intraocular pressure (IOP), number of antiglaucoma eyedrops before and after surgery, as well as complications were measured at all postoperative visits (1 day, 7 days, 6 weeks, 6 months, 12 months). 
 RESULTS: There was a statistically significant decrease in postoperative IOP during the follow-up period. There was no significant difference in the number of medications being used after 6 weeks follow-up. Six months and 12 months after surgery, the number of antiglaucoma eyedrops decreased significantly. Complications were fibrinotic iritis in 4 eyes (5.9%), cystoid macular edema in 3 eyes (4.4%), and hyphema in 1 eye (1.4%). Fibrinotic iritis and macular edema were present in only 37 of 69 eyes that were treated with prostaglandin analogues.
 CONCLUSIONS: Small-incision cataract surgery combined with trabecular aspiration in cases of PEX associated with cataract is effective in IOP reduction over a 1-year follow-up. Prostaglandin analogues may increase the risk of postoperative macular edema and fibrinotic iritis. Preoperative medication exchange may be considered.

Evaluation of the impedance tonometers TGDc-01 and iCare according to the international ocular tonometer standards ISO 8612.

BACKGROUND: Two new tonometers have been introduced that are based on the impedance principle. Both the TGDc-01 (transpalpebral measurement) and the iCare (corneal measurement) do not require corneal anaesthesia. The present work presents an evaluation of both devices. METHODS: Comparative measurements using one of the new tonometers and applanation tonometry were performed by one investigator according to the international standard for ocular tonometer (ISO 8612). Measurements were performed on 445 eyes without corneal pathology from 243 patients. Six measurements were performed for iCare and 3 for TGDc, immediately followed by 3 applanation tonometry measurements. RESULTS: The correlation coefficient with respect to applanation tonometry was 0.81 for TGDc and 0.95 for iCare. TGDc-01 measurements showed an average deviation of 3.1 +/- 2.6 mmHg to those of Perkins applanation tonometry. The maximum difference was 28.7 mmHg below and 9.8 mmHg above the results of applanation tonometry. iCare showed an average deviation of 2.5 +/- 1.1 mmHg to Goldmann tonometry. The maximum difference was 14.5 mmHg below and 9.8 mmHg above. CONCLUSIONS: The results of both new tonometers showed a good correlation with the reference applanation tonometric methods, but the strict requirements of ISO 8612 are not fulfilled by either tonometer at present. Additionally, transpalpebral measurements with the TGDc-01 showed unacceptably high variability.

The short-term effect of latanoprost on intraocular pressure and pulsatile ocular blood flow.

PURPOSE: There is evidence that ocular blood flow plays a critical role in the clinical course of glaucoma. Any reduction in ocular blood flow due to topical antiglaucoma treatment should therefore be avoided. This study aimed to evaluate the short-term effect of local latanoprost application on ocular hemodynamics. METHODS: Intraocular pressure (IOP), ocular pulse amplitude (OPA), ocular pulse volume (OPV), systemic blood pressure, heart rate and the pulsatile component of ocular blood flow (POBF) were recorded using a pneumotonometer linked to the Langham Ocular Blood Flow System in 24 patients in a prospective, open-label study before and after 1 week of topical latanoprost application in both eyes. Twenty of the subjects had primary open-angle glaucoma and four had ocular hypertension. RESULTS: After 1 week of latanoprost treatment, IOP decreased significantly 6.2 +/- 2.9 mmHg in OD (P < 0.001) and 6.2 +/- 3.2 mmHg in OS (P < 0.001). Pulsatile OBF increased significantly by 201.2 +/- 167.4 microL/min in OD (P < 0.001) and 203.8 +/- 187.3 microL/min in OS (P < 0.001). Ocular pulse amplitude and OPV showed statistically significant increases (P < 0.05 and P < 0.001 respectively). Blood pressure and heart rate did not change significantly. CONCLUSION: Our results indicate that 1 week after latanoprost application, POBF, OPA and OPV were significantly increased in the eyes treated. More information on the perfusion of the optic nerve head is needed before the relevance of these findings to optic nerve head blood flow can be interpreted correctly.