Viscocanalostomy combined with nearly 360-degree suture trabeculotomy for the treatment of primary congenital glaucoma: a preliminary report of a novel technique for trabeculotomy.

PURPOSE: The aim of this study was to determine the preliminary efficacy and safety of a novel technique for trabeculotomy for the treatment of primary congenital glaucoma (PCG). METHODS: This retrospective interventional study was conducted on patients with PCG. Pliability test was performed among 5/0 and 6/0 polypropylene sutures and the flexible illuminated microcatheter. Viscocanalostomy was first performed and the Schlemm's canal was identified. Then, suture trabeculotomy was completed except the region for viscocanalostomy. The preoperative and follow-up data were recorded and analyzed. Success criteria were defined as intraocular pressure (IOP) ≤ 21 mmHg without (complete success) or with medications (qualified success). RESULTS: 5/0 polypropylene suture was an appropriate option for cannulation of Schlemm's canal. A total of 33 eyes from 23 consecutive patients were included with a mean follow-up of 9.3 ± 3.6 months (range 6-18 months). Circumferential cannulation by suture was successfully performed in 28 eyes (84.8%) of 18 patients. Mean IOP decreased from 33.9 ± 9.4 mmHg preoperatively to 10.5 ± 3.5 mmHg at 6 months (p < 0.001) and 11.3 ± 4.1 mmHg at 9 months (p < 0.001). Complete success rate was 92.9% [95% confidence interval (CI:0.83-1.03)] and 87.5% (CI:0.69-1.06) at 6 months and 9 months, respectively. Hyphema was found in 5 eyes (17.9%), all of which were absorbed within 1 week. No other complications were observed. CONCLUSIONS: Viscocanalostomy combined with nearly 360-degree suture trabeculotomy as a novel technique controls IOP in patients with PCG without any severe complications. It is suitable for extended applications because of accurate identification of Schlemm's canal and low cost.

Role of CYP1B1, p.E229K and p.R368H mutations among 120 families with sporadic juvenile onset open-angle glaucoma.

BACKGROUND: To determine the frequency of CYP1B1 p.E229K and p.R368H, gene mutations in a cohort of sporadic juvenile onset open-angle glaucoma (JOAG) patients and to evaluate their genotype/phenotype correlation. METHODS: Unrelated JOAG patients whose first-degree relatives had been examined and found to be unaffected were included in the study. The patients and their parents were screened for p.E229K and p.R368H mutations. The phenotypic characteristics were compared between probands carrying the mutations and those who did not carry these mutations. RESULTS: Out of 120 JOAG patients included in the study, the p.E229K mutation was seen in 9 probands (7.5%) and p.R368H in 7 (5.8%). The average age of onset of the disease (p = 0.3) and the highest untreated IOP (p = 0.4) among those carrying mutations was not significantly different from those who did not have these mutations. The proportion of probands with angle dysgenesis among those with p.E229K and p.R368H mutations was 70% (11 out of 16) in comparison to 65% (67 out of 104) of those who did not harbour these mutations (p = 0.56). Similarly, the probands with moderate to high myopia among those with p.E229K and p.R368H mutations was 20% (3 out of 16) in comparison to 18% (18 out of 104) of those who did not harbour these mutations (p = 0.59). CONCLUSION: The frequency of p.E229K and p.R368H mutations of the CYP1B1 gene is low even among sporadic JOAG patients. Moreover, there is no clinical correlation between the presence of these mutations and disease severity.

CYP1B1 Mutations in Individuals With Primary Congenital Glaucoma and Residing in Denmark.

PURPOSE OF THE STUDY: Primary congenital glaucoma (PCG OMIM 231300) can be caused by pathogenic sequence variations in cytochrome P450, subfamily 1, polypeptide 1 (CYP1B1). The purpose of this study was to investigate the contribution of sequence variations in CYP1B1 in a cohort of individuals with PCG residing in Denmark. METHODS: The study included 37 unrelated individuals with PCG. Individuals were investigated for CYP1B1 mutations by Sanger sequencing of polymerase chain reaction products using BigDye terminators and capillary electrophoresis. RESULTS: A total of 12 mutations were identified and 5 of these were novel. Six were missense mutations; 4 were truncating mutations (2 nonsense and 2 frameshift); 1 was an in-frame deletion and 1 was an in-frame duplication. Mutations in CYP1B1 could fully explain the PCG phenotype in 7 individuals (18%). Five individuals were compound heterozygous or presumed compound heterozygous, 1 was homozygous and 1 was apparently homozygous. Three individuals were heterozygous for sequence variations in CYP1B1 thought to be pathogenic-one of these was p.(Tyr81Asn). Several known sequence variations with presumably no functional effect were found in the cohort. CONCLUSIONS: In this study, we identified 12 CYP1B1 mutations, 5 of which were novel. The frequency of CYP1B1 mutations in this cohort was comparable with other populations. We also detected an individual heterozygous for p.(Tyr81Asn) mutation, previously suggested to cause autosomal dominant primary open-angle glaucoma.

¿Sirve para algo la lente de Goldman en el glaucoma por cierre angular? / Is the Goldman lens any good in angle-closure glaucoma?

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A case of spontaneously resolved primary congenital glaucoma.

Primary congenital glaucoma usually presents as enlarged and hazy cornea at birth or early childhood. The diagnosis is based on a thorough clinical examination under anesthesia. Most cases require surgical intervention as the definitive treatment. In very rare instances, primary congenital glaucoma may arrest and resolve spontaneously. We describe a case of spontaneously arrested and resolved primary congenital glaucoma in a 37-year-old male presenting with large cornea, Haab's striae, and normal intraocular pressure in one eye. Such a case has not been previously described from the Indian subcontinent.

Clinical Variability of Primary Congenital Glaucoma in a Spanish Family With Cyp1b1 Gene Mutations.

BACKGROUND: Primary congenital glaucoma (PCG) is a rare disease. In around a third of Spanish patients, the disease is attributed to mutations in the CYP1B1 gene inherited in an autosomal recessive manner. Such mutations are the main known genetic cause of PCG. CASE REPORT: We describe the case of a family with 3 of 7 siblings diagnosed with PCG. In a genetic study of the CYP1B1 gene, 2 null mutations were identified in the affected siblings (R355fsX69/T404fsX38). Two of the 4 healthy siblings were heterozygous for mutation R355fsX69 and the remaining 2 had no mutations. The healthy parents were found to be heterozygous for mutations T404fsX38 (mother) and R355fsX69 (father). High variation in the expression of PCG was observed, especially in terms of disease onset and severity: Patient 1 in the eldest affected sibling, PCG was diagnosed at 8 years of age and is presently stable after 60 months of medical treatment; patient 2 the second affected child underwent surgery at 7 days of age. Today, at 104 months, she has undergone 2 operations on the right eye and 3 on the left eye; patient 3 the youngest sibling, the disease also manifested at birth and the boy underwent surgery at 4 days. Currently he is 84 months old, he has required 7 operations for glaucoma, 3 in the right eye and 4 in the left. CONCLUSIONS: This clinical case reveals the etiological relationship between CYP1B1 mutations and PCG. In addition, it indicates a highly variable clinical picture associated with a single disease genotype mainly affecting disease onset and progression.

Efficacy and safety of deep sclerectomy in childhood glaucoma in Saudi Arabia.

PURPOSE: To evaluate the efficacy and safety of deep sclerectomy in childhood glaucoma. METHODS: A prospective cohort of 120 children presenting with glaucoma to King Abdul Aziz University Hospital (KAUH) was subjected to nonpenetrating deep sclerectomy surgery (NPDS). Eventually, 57 patients had macro perforation and converted to penetrating deep sclerectomy (PDS). Intra-operative mitomycin C (MMC) 0.2 mg/ml was used in all patients. Pre- and postintervention glaucoma indices were assessed. Complete success rate (CSR) was identified as achieving an end-point of intraocular pressure <21 without any antiglaucoma medications. Data were analysed to compare pre- and postintervention changes and to compare both procedures. RESULTS: After follow-up of 35.8 (34.5) months, NPDS procedure went smooth in 74 eyes of 63 patients. The complete success rate was 79.7%, whereas the overall success rate was 82.4%. Thirteen cases failed. The probability to survive was 74.6% after the 12th month. The mean intraocular pressure (IOP) went down to 11.5 ± 3.0 mmHg compared to 31.9 mmHg preoperatively. Comparing cases with NPDS to those with PDS, the magnitude of IOP reduction (15.8) was higher than that of the PDS (14.8); however, this difference was not statistically significant (p = 0.259). Apart from involuntary perforation of trabeculodescemetic window (TDW), neither intra-operative nor early postoperative complications were observed. CONCLUSIONS: Deep sclerectomy in childhood glaucoma can effectively reduce the IOP, without the occurrence of serious complications that are commonly seen after trabeculotomy or combined trabeculotomy trabeculectomy.

Corneal changes assessed using confocal microscopy in patients with unilateral buphthalmos.

PURPOSE: To compare corneal structures in buphthalmic eyes and healthy eyes in patients with unilateral congenital glaucoma using a corneal confocal microscope. METHODS: Ten patients with unilateral buphthalmos (mean ± SD age, 14.85 ± 5.12 years) were examined using corneal confocal microscopy. The cell density and cell area of endothelial cells and superficial and basal epithelial cells and the number of keratocytes were evaluated. RESULTS: There was no significant difference between the cell density of superficial epithelial cells in buphthalmic eyes relative to healthy eyes (P = 0.1944). The cell density of basal epithelial cells was significantly higher (P = 0.0234) and the cell area was significantly smaller (P = 0.0181) in buphthalmic eyes relative to healthy eyes. There was no difference between the number of keratocytes in buphthalmic eyes and healthy eyes in the anterior stroma (P = 0.273) or in the posterior stroma (P = 0.0799). The cell density of endothelial cells was significantly lower and the cell area was significantly larger in buphthalmic eyes relative to healthy eyes (P = 0.0009). CONCLUSIONS: We demonstrated a lower cell density of endothelial cells in buphthalmic eyes. We found no differences in keratocyte density between the buphthalmic eyes and healthy eyes. The cell density of basal epithelial cells was higher in buphthalmic eyes. These differences could be due to buphthalmos or due to the previous surgical and medical therapies. Monitoring of these changes could help to contribute to accurate assessments regarding future ocular surgical procedures.

Mitochondrial dysfunction in glaucoma: understanding genetic influences.

Glaucoma is the leading cause of irreversible blindness worldwide. This review aims to provide a greater understanding of the complex genetic influences that may lead to mitochondrial dysfunction and increase susceptibility to retinal ganglion cell (RGC) loss in primary open angle glaucoma (POAG), and thus elucidate potentially important pathophysiological pathways amenable to therapeutic intervention. Emerging evidence from genome wide association and other genetic studies suggests that changes in the mitochondrial DNA (mtDNA) and in nuclear DNA genes that encode mitochondrial proteins may influence mitochondrial structure and function and, therefore, contribute to the pathogenesis of POAG. We propose that a variety of genes (OPA1, MFN1, MFN2, CYP1B1, PARL, SOD2, SRBD1, GST, NOS3, TNFa and TP53) may each confer a background susceptibility to POAG in different populations having one common link: mitochondrial dysfunction. The relationship between polymorphisms in these genes and increasing risk for POAG is presented and the limitations of the available current knowledge are discussed.

Mutation spectrum of the CYP1B1 gene for congenital glaucoma in the Japanese population.

PURPOSE: Mutations of the CYP1B1 gene cause primary congenital glaucoma (PCG), Peters anomaly, and juvenile open-angle glaucoma (JOAG). The aim of this study was to determine the spectrum and role of the CYP1B1 gene in Japanese patients with PCG or JOAG. METHODS: Genomic DNA was extracted from the leukocytes of 18 unrelated patients with PCG and 21 unrelated patients with JOAG. All of the patients developed high intraocular pressure (IOP) before the age of 35 years. One hundred unrelated healthy adults with normal IOP were examined in the same way. The three exons of the CYP1B1 gene were amplified by polymerase chain reaction and directly sequenced. RESULTS: Mutational screening and sequence analyses of the CYP1B1 gene revealed four mutations in four patients with PCG: p.Asp192Val, c.4776insAT, p.Val364Met, and p.Asp430Glu. The first three mutations have been reported in other Japanese PCG patients, but Asp430Glu is a new mutation. No mutations were found in the CYP1B1 gene of the JOAG patients. CONCLUSIONS: PCG in approximately 20% of Japanese patients may be associated with CYP1B1 mutations, but JOAG is not. The three mutations p.Asp192Val, c.4776insAT, and p.Val364Met appear to be common in the Japanese population and might be useful in genetic screening for PCG.

Variable expressivity and high penetrance of CYP1B1 mutations associated with primary congenital glaucoma.

OBJECTIVE: To investigate penetrance and expressivity of CYP1B1 genotypes associated with primary congenital glaucoma (PCG). DESIGN: Observational case series, systematic review, and comparative analysis of the literature. PARTICIPANTS: Forty probands affected with PCG, 16 siblings affected with PCG, and 103 siblings and 75 parents of the probands reported not to be affected by history. The participants were members of 40 unrelated families. METHODS: Mutations were screened by restriction fragment length polymorphism, allele-specific polymerase chain reaction amplification, and direct sequencing. Ophthalmologic examination included slit-lamp biomicroscopy, intraocular pressure (IOP) measurement, gonioscopy, and high magnification stereoscopic fundus examination, followed by standard achromatic perimetry. MAIN OUTCOME MEASURES: Identification of subjects carrying CYP1B1 mutations. Glaucoma diagnosis based on slit-lamp examination, IOP measurement, gonioscopic findings, optic nerve appearance, and perimetry. RESULTS: Fifteen different homozygous or compound heterozygous mutant CYP1B1 genotypes were identified. Most probands and previously diagnosed subjects harbored G61E, R368H, R390H, and R469W mutations. Among the 178 apparently unaffected family members, 20 subjects from 12 families were observed to harbor 2 CYP1B1 mutations, suggesting an average penetrance of 73% for all the mutations. These 20 subjects ranged in age from 14 to 54 years. R390H appeared to have a notably high penetrance. Penetrance was 50% in the subset of families with incomplete penetrance. Ophthalmologic examination on 14 of the 20 apparently nonpenetrant individuals showed that 8 subjects were affected with juvenile open-angle glaucoma (JOAG) or primary open-angle glaucoma (POAG), and that 3 subjects were glaucoma suspect. One of the individuals with a JOAG diagnosis was the identical twin sibling of a proband affected with PCG. CONCLUSIONS: At least 57% of the PCG nonpenetrant individuals examined clinically were affected with JOAG or POAG to varying degrees, and overall penetrance of "affected CYP1B1 genotypes" with respect to glaucoma may be more than 90%. These findings suggest that "affected CYP1B1 genotypes" exhibit variable expressivity rather than nonpenetrance. The clinical implication of this observation is that seemingly unaffected relatives of patients with PCG, particularly those known to harbor CYP1B1 mutations, should undergo regular ophthalmologic examination to allow early diagnosis.

[Genetic variants of CYP1B1 and WDR36 in the patients with primary congenital glaucoma and primary open angle glaucoma from Saint-Petersburg].

In 32 patients with primary congenital glaucoma (PCG), a search for mutations in the myocilin (MYOC), cytochrome P450B1 (CYP1B1), and WDR36 genes was performed. The Q368X mutation in myocilin gene, typical of the patients with adult-onset primary open-angle glaucoma (POAG), was not detected in the PCG patients. Screening of the CYP1B1 introns 2 and 3 for the presence of mutations in PCG patients revealed only six DNA polymorphisms, including IVS1-12ntT>C (g.3793 T>C), A119S (g.4160 G>T; GCC>TCC), G188G (g.4369 C>A; GGC>GGA), L432V (G.8131 C>G; CTG>GTG), D449D (g.8184 C>T; GAC>GAT), and N453S (g.8195 A>G; AAC>AGC) (nucleotide numbering is given in accordance with the GenBank sequence U56438). In the groups of PCG patients and donors without eye diseases, the frequencies of these variants were not statistically significantly different, pointing to the neutrality of these polymorphisms. Furthermore, the CYP1B1 polymorphism L432V, considered to be associated with POAG in some world populations, was not associated with this disease in the patients from St. Petersburg. DNA collections obtained from the POAG and PCG patients and from the control group were tested for the carriage of the worldwide distributed mutations of the WRD36 gene, D658G, R529Q, A449T, and N355S. D658G variant was found with equally low frequencies in the groups of POAG and PCG patients, as well as in the control group. Mutations A449T and R529Q were found only once each, while mutation N355S was not detected in any of the groups examined. Our results indicate that the WDR36 variants make no substantial contribution to the development of POAG and PCG in the patients from St. Petersburg and represent normal DNA polymorphism. It is likely that in most of the PCG patients from the population examined the disease is not associated with the CYP1B1 gene defects.

Flap suture--a simple technique for the revision of hypotony maculopathy following trabeculectomy with mitomycin C.

BACKGROUND: A serious complication following trabeculectomy with mitomycin C (MMC) is intraocular hypotony with hypotony maculopathy, papilledema, flattening of the anterior chamber, corneal decompensation and a decrease in visual acuity. We describe a new simple surgical technique for the treatment of hypotony maculopathy following trabeculectomy with MMC. METHODS: In a prospective consecutive case study, 16 patients with hypotony maculopathy following trabeculectomy with MMC were included. Through the intact conjunctiva, additional 10.0 nylon sutures were placed through the scleral flaps into the adjacent sclera. Assessment of visual acuity, intraocular pressure (IOP) measurement and fundoscopy were performed on the 1st and 7th day postoperatively and 1, 3 and 6 months postoperatively. Photography of the bleb and the posterior pole and optical coherence tomography imaging of the posterior pole were performed. RESULTS: Before surgery (flap suture), the mean IOP was 2.8 mmHg (+/-1.1; range from 1 to 4 mmHg). It was 24.9 +/- 11.7 mmHg (range; 9-48 mmHg) on the 1st postoperative day, 15.7 +/-8.1 mmHg (range; 5-35 mmHg) on day 7, 11.1 +/-4.1 mmHg (range; 5-20 mmHg) 1 month after surgery, 9.3 +/-3.9 mmHg (range; 2-20 mmHg) after 3 months, and 9.6 +/-4.2 mmHg (range; 2-20 mmHg) after 6 months. The best corrected mean visual acuity was 20/50 before trabeculectomy and 20/160 before flap suture. It improved to 20/63 at 6 months postoperatively. Clinical signs of hypotony maculopathy disappeared in all patients. No bleb leakage was observed in any patient during follow-up. CONCLUSION: Resuturing the scleral flap through the intact conjunctiva is an effective and minimally invasive method to treat hypotony maculopathy following trabeculectomy with MMC. Thus, opening the conjunctiva can be avoided.

Prevalence of CYP1B1 mutations in Australian patients with primary congenital glaucoma.

Analysis of CYP1B1 in primary congenital glaucoma (PCG) patients from various ethnic populations indicates that allelic heterogeneity is high, and some mutations are population specific. No study has previously reported the rate or spectrum of CYP1B1 mutations in Australian PCG patients. The aim of this study is to determine the frequency of CYP1B1 mutations in our predominately Caucasian, Australian cohort of PCG cases. Thirty-seven probands were recruited from South-Eastern Australia, along with 100 normal control subjects. Genomic DNA was extracted and the coding regions of CYP1B1 analysed by direct sequencing. Sequence analysis identified 10 different CYP1B1 disease-causing variants in eight probands (21.6%). Five subjects were compound heterozygotes, two subjects heterozygous and one homozygous for CYP1B1 mutations. Three missense mutations are novel (D192Y, G329D, and P400S). None of the novel mutations identified were found in normal controls. One normal control subject was heterozygous for the previously reported CYP1B1 R368H mutation. Six previously described probable polymorphisms were also identified. Mutations in CYP1B1 account for approximately one in five PCG cases from Australia. Our data also supported the high degree of allelic heterogeneity seen in similar studies from other ethnic populations, thereby underscoring the fact that other PCG-related genes remain to be identified.

Excimer laser trabeculotomy: a new, minimally invasive procedure for patients with glaucoma.

BACKGROUND: Excimer laser trabeculotomy (ELT) ab interno is a new surgical technique to reduce intraocular pressure (IOP) in patients with glaucoma or ocular hypertension. Our purpose was to examine IOP reduction and the use of antiglaucoma drugs (AGD) in patients treated with ELT and to evaluate the safety of this laser treatment. METHODS: To increase the outflow of aqueous humor, ten microperforations of the trabecular meshwork were performed by an endoscope-guided photoablative laser probe (Excimer laser, AIDA, TUI-Laser, Munich; pulse energy: 1.2 mJ at fiber tip, pulse duration: 60 ns, repetition rate: 20 Hz). Average operation time usually was about 2 min. In our pilot study, one group of patients without cataract underwent ELT, the other group with cataract underwent phacoemulsification (PHACO) plus ELT. IOP, visual acuity, and AGD were determined preoperatively (T0) and 2-4 months (T1), 5-7 months (T2), 11-13 months (T3), and 22-26 (T4) months after surgery. Treatment was defined to be successful if (1) postoperative IOP was < or =21 mmHg, and (2) IOP reduction was at least 20%. RESULTS: ELT reduced the IOP from 24.1+/-0.7 (n=69) mmHg preoperatively to 18.8+/-0.4 (T1, n=66), 20.0+/-0.5 (T2, n=51), 18.8+/-0.8 (T3, n= 37), and 16.8+/-1.0 (T4, n=15) mmHg, respectively. However, 28% of the eyes needed repeat surgery due to insufficient IOP reduction. According to Kaplan-Meier statistics, the success rate was 60% (T1), 49% (T2), and 46% (T3), respectively. The number of AGD was 1.9+/-0.1 (T0), 1.2+/-0.2 (T1), 1.3+/-0.2 (T2), 1.8+/-0.2 (T3), and 1.5+/-0.3 (T4). Combined phacoemulsification plus ELT reduced the IOP from 22.4 mmHg+/-0.6 (T0, n=57) to 16.5+/-0.4 (T1, n=52), 16.1+/-0.5 (T2, n= 40), 16.4+/-0.4 (T3, n= 35), and 12.8+/-1.5 (T4, n=4) mmHg, respectively; 7% of the eyes treated with the combined procedure needed repeat surgery due to insufficient IOP reduction. According to Kaplan-Meier statistics, the success rate was 85% (T1), 74% (T2), and 66% (T3), respectively. The number of AGD was 1.1+/-0.2 (T0), 0.9+/-0.2 (T1), 1.1+/-0.2 (T2), 1.2+/-0.2 (T3), and 1.8+/-0.9 (T4). CONCLUSIONS: ELT, especially in combination with phacoemulsification, is a new, promising, minimally invasive laser treatment to reduce IOP for at least 1-2 years. ELT alone is less effective in IOP reduction.

Gln48His is the prevalent myocilin mutation in primary open angle and primary congenital glaucoma phenotypes in India.

PURPOSE: Myocilin gene defects have been originally implicated in primary open angle glaucoma (POAG). Based on multiple reports for the occurrence of Gln48His mutation (c.144G>T; HGMD accession number CM023962) among Indian POAG patients, we wanted to estimate the prevalence of this mutation in primary open angle and primary congenital glaucoma (PCG) in India and assess its role in the causation of the disease. METHODS: Two hundred cases each of POAG and PCG were screened for the Gln48His mutation by RFLP (AccI) analysis of the PCR amplicons followed by confirmation of the c.144G>T change by direct sequencing. RESULTS: The Gln48His mutation was detected in 9 different glaucoma patients (four POAG and five PCG). While all four POAG cases were heterozygous, among PCG cases, four were heterozygous and one exhibited homozygous genotype for the mutation. One each of POAG and PCG patients was detected to be heterozygous for CYP1B1 mutation (c.1656C>T, Pro437Leu) and (c.1449G>A, Arg368His), respectively. None of the 300 ethnically matched normal controls contained either the MYOC or CYP1B1 mutation(s). CONCLUSIONS: The myocilin mutation, Gln48His, represents an allelic condition involving a spectrum of glaucoma phenotypes in Indian populations, and could be a potential risk factor towards disease predisposition among patients of Indian origin. The study also highlights the role of MYOC as a candidate in different glaucoma subtypes that needs to be investigated further.

[Primary infantile glaucoma with late diagnosis--case report]. / Glaucom infantil primitiv diagnosticat tardiv--caz clinic.

Congenital glaucoma is a very rare condition, and the subtype infantile glaucoma (late-onset congenital glaucoma) represent 50% of it. We present a case of neglected infantile glaucoma and the difficulties in therapeutic management.