Enzyme-induced posterior vitreous detachment in the rat produces increased lens nuclear pO2 levels.

It has been proposed that disruption of normal vitreous humor may permit O(2) to travel more easily from the retina to the center of the lens where it may cause nuclear cataract (Barbazetto, I.A., Liang, J., Chang, S., Zheng, L., Spector, A., Dillon, J.P., 2004. Oxygen tension in the rabbit lens and vitreous before and after vitrectomy. Exp. Eye Res. 78, 917-924; Harocopos, G.J., Shui, Y.B., McKinnon, M., Holekamp, N.M., Gordon, M.O., Beebe, D.C., 2004. Importance of vitreous liquefaction in age-related cataract. Invest. Ophthalmol. Vis. Sci. 45, 77-85). In the present study, we injected enzymes intravitreally into guinea pigs (which possess an avascular retina) and rats (which possess a vascular retina) to produce either vitreous humor liquefaction plus a posterior vitreous detachment (PVD) (with use of microplasmin) or vitreous humor liquefaction only (with use of hyaluronidase), and 1-2 weeks later measured lens nuclear pO(2) levels in vivo using a platinum-based fluorophore O(2) sensor (Oxford-Optronix, Ltd.). Experiments were also conducted in which the animals were allowed to breathe 100% O(2) following intravitreal injection with either microplasmin or hyaluronidase in order to investigate possible effects on O(2) exchange within the eye. Injection of guinea pigs with either of the two enzymes produced no significant differences in lens pO(2) levels 1-2 weeks later, compared to controls. However, for the rat, injection of microplasmin produced a 68% increase in O(2) level in the center of the lens, compared to the controls (5.6mm Hg increasing to 9.4mm Hg, p<0.05), with no corresponding effect observed following similar use of hyaluronidase. Treatment of guinea pigs with microplasmin dramatically accelerated movement of O(2) across the vitreal space when the animals were later allowed to breathe 100% O(2) (for example, O(2) traveled to a location directly behind the lens 5x faster than control; p<0.01); however, the effect following treatment with hyaluronidase was significantly less. When microplasmin-injected rats breathed 100% O(2), the time required for O(2) to reach the center of the lens was 3x faster than control (0.4 min compared to 1.4 min, p<0.01). The results have implication with regard to the occurrence of age-related PVD in the human, and a possible acceleration of maturity-onset nuclear cataract. In addition, enzymatic creation of a PVD to increase the rate of O(2) exchange within the vitreal space may have potential application for treatment of retinal ischemic disease.

Retinal detachment in focal dermal hypoplasia.

PURPOSE: Focal dermal hypoplasia is a systemic disease that includes well recognized ocular abnormalities. Retinal detachment has not previously been reported as a part of this syndrome. AIM: To report a case of focal dermal hypoplasia with an associated retinal detachment. METHODS: Single case report of a child with a colobomatous retinal detachment and the focal dermal hypoplasia syndrome. CONCLUSIONS: Retinal detachments may occur as part of the focal dermal hypoplasia syndrome. Expanding knowledge of this syndrome may help ophthalmologists diagnose this rare condition.

Cosegregation of two unlinked mutant alleles in some cases of autosomal dominant familial exudative vitreoretinopathy.

Familial exudative vitreoretinopathy (FEVR) is a bilateral, clinically and genetically heterogeneous hereditary eye disorder that affects both the retina and the vitreous body. The condition has a high degree of penetrance and variable expressivity. In some cases of autosomal dominant FEVR (AD FEVR), mutations in the frizzled-4 gene (FZD-4) have been shown to be involved in FEVR pathology. In this study, we report that a second unlinked gene (Factor V) is also mutated (Leiden mutation) in the same family, which harbors the FZD-4 gene mutation. These results show for the first time that some families with FEVR could be digenic. While this is unlikely to be a widespread problem, the occurrence of digenic disorders with apparently simple Mendelian inheritance patterns renders the current method of analysis of monogenic disorders by linkage and mutation screening incomplete.

Factor V Leiden mutation (R506Q) and the risk of advanced retinopathy of prematurity.

The coagulation factor V Leiden mutation was reported to be a significant (10.7%) risk factor for pre-term deliveries. It is also well known that a portion (10%) of very low birth weight premature babies develop advanced retinopathy of prematurity (ROP) which is a leading cause of blindness in children. However, the relationship between the Leiden mutation and development of advanced ROP is not known. In order to understand this relationship as well as genetic contribution to ROP, in this study, we have analyzed 100 pre-term infants with advanced ROP (stage 4B/5), 20 term babies with a clinically similar disease called familial exudative vitreoretinopathy (FEVR) and 16 normal babies from four different ethnic backgrounds. Our extensive analysis has identified a heterozygous Leiden mutation in four patients (4%) with advanced ROP and in one patient (5%) with sporadic FEVR. DNA sequence analysis has further confirmed this base change as well as heterozygosity. However, the frequency observed in the patients analyzed in our study is lower than reported frequency in the general population (5.4%). Therefore, statistically factor V mutation on its own is not a major risk factor for the above two disorders. However, it may be associated with other additive factors as might be expected for a complex genetic trait.

Enzymatic-assisted vitrectomy.

PURPOSE: This paper discusses the approach of enzymatic vitrectomy and potential applications. METHODS: A description of available agents for enzymatic vitreous surgery will be given and the techniques that have been suggested. RESULTS: Both animal and human results will be presented in this article regarding trials of enzymatic vitreous surgery. CONCLUSION: Enzymatic vitreous surgery may be a useful adjunct or additional agent to treat several vitreoretinal diseases.

Incidence of retinal detachment and visual outcome in eyes presenting with posterior vitreous separation and dense fundus-obscuring vitreous hemorrhage.

PURPOSE: To determine visual outcomes and the incidence of retinal detachment in eyes presenting with posterior vitreous separation and dense fundus-obscuring vitreous hemorrhage. DESIGN: Retrospective consecutive noncomparative interventional case series. PARTICIPANTS: Thirty-six eyes (15 right eyes and 21 left eyes) of 34 patients (18 female and 16 male) ranging in age from 42 to 94 years. Mean follow-up was 14 months. METHODS: A comparison of the best-corrected initial visual acuities versus final visual acuities after spontaneous resolution of vitreous hemorrhage or surgical intervention. The number of eyes that were found to have retinal tears or that had a rhegmatogenous retinal detachment develop was documented. Logarithm of the minimum angle of resolution-converted visual acuities was used for comparison. Categorical data were analyzed by Fisher's exact test, and population means were compared by Student's t test. MAIN OUTCOME MEASURES: Final mean visual acuities, number of eyes with at least one retinal tear, location of retinal tears, number of eyes that had retinal detachment develop, and the number of eyes repaired with scleral buckling surgery and/or pars plana vitrectomy. RESULTS: Twenty-four of 36 eyes (67%) were found to have at least one retinal break (range, 0-4 breaks), with 88% of breaks located in the superior retina. Eleven eyes (31%) had more than one retinal break. Fourteen of 36 eyes (39%) had a rhegmatogenous retinal detachment develop that was repaired with pars plana vitrectomy and scleral buckling. An additional 14 eyes (39%) underwent vitrectomy for nonclearing vitreous hemorrhage. The incidence of retinal detachment in eyes with a history of retinal detachment in the contralateral eye was 75% (P = 0.04). Seven of 14 eyes (50%) with retinal detachment had coexisting proliferative vitreoretinopathy. Most retinal breaks and detachments occurred in emmetropic or myopic eyes. For all 36 eyes the mean preoperative visual acuity was 20/1233, and the mean final visual acuity was 20/62 (P < 0.0001). Eyes that had a macula-off retinal detachment develop had worse final visual outcomes (20/264; P = 0.01), as did eyes that had proliferative vitreoretinopathy develop (20/129; P = 0.04). CONCLUSIONS: Acute, spontaneous, nontraumatic posterior vitreous separation with dense fundus-obscuring vitreous hemorrhage is associated with a high incidence of retinal tears and detachment. Close follow-up with clinical examination and ultrasonography is necessary, because many of these eyes may eventually require surgical intervention. Aggressive management with early vitrectomy should be considered when there is a history of retinal detachment in the contralateral eye.

Lens-sparing vitreous surgery for tractional stage 4A retinopathy of prematurity retinal detachments.

PURPOSE: To assess the efficacy of lens-sparing vitrectomy in tractional 4A retinopathy of prematurity (ROP) retinal detachments in reducing progression to stage 4B or 5 ROP. DESIGN: Retrospective, noncomparative consecutive case series. PARTICIPANTS: Forty eyes (31 patients) with stage 4A ROP at 38 to 42 weeks post-conceptional age. INTERVENTION: Lens-sparing vitrectomy. MAIN OUTCOME MEASURES: Retinal attachment status and presence/absence of fixation behavior. RESULTS: The range of follow-up was 6 to 22 months (mean, 12 months). Ninety percent (36 of 40) of eyes showed retinal reattachment and fixation behavior at their last follow-up visit. CONCLUSIONS: These results suggest that vitreous surgery can interrupt progression of ROP from stage 4A to stages 4B or 5.

Autologous plasmin enzyme in the surgical management of diabetic retinopathy.

PURPOSE: This is a pilot study to assess the use of autologous plasmin enzyme (APE) as an adjunct to vitreous surgery in eyes with advanced diabetic retinopathy. DESIGN: Prospective noncomparative interventional case series. PARTICIPANTS: Seven patients with advanced diabetic retinopathy selected at random from our practice population. METHODS: Seven eyes were treated with APE as an adjunct to standard vitreous surgery. Six eyes had macular tractional retinal detachments, and one eye had refractory macular edema. Three fellow eyes had standard vitreous surgery performed for macular tractional retinal detachments without APE. All 10 eyes had macular edema and background diabetic retinopathy. MAIN OUTCOME MEASURES: The main outcome measures included induction of a posterior vitreous detachment, retinal reattachment, improvement in visual acuity, and resolution of macular edema. RESULTS: All seven APE-treated eyes achieved spontaneous or easy removal of the posterior hyaloid including one eye that had vitreoschisis over areas of detached retina. All eyes treated with APE had resolution of intraretinal edema. Retinas of all eyes treated with APE were reattached. The three fellow eyes were treated by vitreous surgery without APE. Two of the three fellow eyes had reattached retinas, but none had resolution of intraretinal edema without further focal photocoagulation treatment. Mean visual acuity improvement was 0.7 logarithm of the minimum angle of resolution (LogMAR) units in APE-treated eyes and 0.1 LogMAR units in eyes without APE. The average follow-up period was 14 months. CONCLUSIONS: This pilot study suggests that APE may be beneficial in the surgical management of diabetic retinopathy.

Adult retinopathy of prematurity: outcomes of rhegmatogenous retinal detachments and retinal tears.

PURPOSE: To describe the results of retinal tears and rhegmatogenous retinal detachments (RD) in adults with retinopathy of prematurity (ROP). DESIGN: Noncomparitive interventional case series. METHODS: Retrospective cohort of 216 eyes of 108 patients, 15 years or older, followed for up to 23 years (median, 6.2 years). RESULTS: One eye was initially seen with an RD, and during follow-up 30 eyes had an RD develop. An additional surgical procedure was required in 7 of the 31 eyes (23%) with an RD. Four eyes were initially seen with retinal tears, and during follow-up 19 eyes had a retinal tear develop. Seven of the 23 eyes (30%) with a retinal tear had initial repair fail. Eyes with minimal cicatricial changes from ROP were still at high risk for tears and detachments developing. Eighty percent of eyes with retinal tears and 60% of eyes with an RD that started with vision >20/60 maintained that level of vision at the final examination. CONCLUSION: In patients with a history of premature birth, features of fundus examinations do not correlate with the occurrence of a retinal tear or RD. Repair of a tear or detachment in such a patient is more likely to require multiple procedures but can still be associated with good visual results. Physicians should consider widespread relief of vitreoretinal traction for a tear or detachment in any patient with a history of premature birth.

Insertion and deletion mutations in the dinucleotide repeat region of the Norrie disease gene in patients with advanced retinopathy of prematurity.

Retinopathy of prematurity (ROP) is a leading cause of blindness in premature children. It is a multifactorial disorder which causes fibrovascular tissue changes that affect the retina in low birth-weight and short gestational age infants. To determine the prevalence of Norrie disease (ND) gene mutations, clinical examination and molecular genetic analyses were performed in 100 pre-term babies of different ethnic backgrounds who developed advanced ROP. The leukocyte DNA was extracted, amplified by the polymerase chain reaction (PCR), and analyzed by single-strand conformation polymorphism (SSCP), G/T and C/A scanning, and by DNA sequencing. All three exons, including splice sites and the 3'-untranslated region, were screened. Of the 100 patients analyzed, 2 patients with advanced ROP showed a mobility shift in the DNA. In 1 patient, this mobility shift was caused by the insertion of an additional 12-bp CT repeat in exon 1, and in the second patient, there was a 14-bp deletion in the same exon of the ND gene, as evidenced by direct sequencing of the amplified products. Similar analyses of exons 2 and 3 and the 3'-untranslated region failed to detect additional mutations in the gene. None of the 130 normal, unrelated controls revealed similar changes. Taking into account the above results, as well as those of other studies, it appears that the ND gene mutations can account for 3% of cases of advanced ROP. Although the ND gene is not frequently involved in advanced ROP, the present large-scale study further supports the hypothesis that genetic influences may play an important role in the development of severe ROP in some premature infants.

Evaluation of RP2 and RP3 genes in an X-linked RP family manifesting loss of central vision and preserved peripheral function.

X-Linked retinitis pigmentosa is a most severe and heterogeneous disorder of the retina. Recently, genes (RP2 and RPGR) from two X-linked loci have been positionally cloned and mutations have been identified in many families. To further evaluate allelic and non-allelic heterogeneity and the genotype--phenotype relationships, and to determine the prevalence of mutations in the gene, we have analyzed one previously unreported X-linked retinitis pigmentosa family, using a combination of haplotype analysis and DNA sequencing. Our extensive analysis of the RP2 gene failed to detect any disease--causing or polymorphic mutations. In the case of the RP3 gene, the alleles of the dinucleotide repeat marker did not segregate with the disease. Although we cannot completely exclude the possibility of the RP2 and RP3 genes as candidate genes, the above results suggest that structural and functional changes associated with the RP2 gene are not responsible for the phenotype in the family analyzed. Further identification of the X-linked genes may facilitate the elucidation of the molecular basis of the disorder in the family analyzed.

X-linked juvenile retinoschisis: mutations at the retinoschisis and Norrie disease gene loci?

Juvenile retinoschisis (RS) and Norrie disease (ND) are X-linked recessive retinal disorders. Both disorders, in the majority of cases, are monogenic and are caused by mutations in the RS and ND genes, respectively. Here we report the identification of a family in which mutations in both the RS and ND genes are segregating with RS pathology. Although the mutations identified in this report were not functionally characterized with regard to their pathogenicity, it is likely that both of them are involved in RS pathology in the family analyzed. This suggests the complexity and digenic nature of monogenic human disorders in some cases. If this proves to be a widespread problem, it will complicate the strategies used to identify the genes involved in diseases and to develop methods for intervention.

Coats' disease and congenital retinoschisis in a single eye: a case report and DNA analysis.

The clinical features of Coats' disease and congenital retinoschisis (RS) are distinctly different. Therefore, finding changes consistent with Coats' disease and congenital RS in a single eye is an unusual occurrence. The following report describes two cases with a Coats' telangiectatic lesion in one region of the retina separated by normal retina and the presence of central and peripheral congenital RS. Molecular genetic analysis of the Norrie disease and RS genes failed to identify disease-causing or polymorphic mutations in either of the genes, suggesting that the above condition is clinically and genetically a different disorder. Further studies are needed to identify the genes responsible for the above disorder and associated ocular manifestations.

Clinical course and surgical treatment of macular epiretinal membranes in young subjects.

OBJECTIVE: To examine the surgical and nonsurgical visual outcomes of young subjects with idiopathic macular epiretinal membranes (ERMs). DESIGN: Retrospective observational and noncomparative interventional case series. PARTICIPANTS: Nineteen consecutive subjects (20 eyes) aged 40 years or less with an idiopathic macular ERM. METHODS: Group 1: 10 consecutive eyes were initially seen with visual acuity of 20/50 or better; 7 eyes were observed, and 3 eyes with progressive visual loss to <20/50 underwent vitrectomy and membrane peeling. Group 2: 10 consecutive eyes with presenting visual acuity of 20/60 or worse underwent vitrectomy and membrane peeling. MAIN OUTCOME MEASURES: Visual acuity, cataract formation, ERM recurrence, operative complications. RESULTS: Group 1: With no surgery, visual acuity remained stable or improved in 5 of 10 eyes (50%), with a mean follow-up of 3.7 years. Three of 10 eyes (30%) had visual loss < or =20/60 develop and underwent vitrectomy. Postoperative visual acuity improved an average of 6 lines with a mean follow-up of 17.6 months. Group 2: After vitrectomy, visual acuity improved 2 or more lines in 7 of 10 eyes (70%), with a mean improvement of 4.4 lines and mean follow-up of 29.2 months. Groups 1 and 2: Three of 13 eyes (23%) that underwent vitrectomy had recurrent ERM formation. CONCLUSIONS: Young subjects with idiopathic macular ERMs and a presenting visual acuity of 20/50 or better had a favorable visual outcome with observation. Subjects with an initial vision of 20/60 or worse, or those who had a visual decrease to < or =20/60 had significantly improved visual acuity after vitrectomy. ERM recurrence is relatively high after surgery.

A comparison of visual results and complications in eyes with posterior chamber intraocular lens dislocation treated with pars plana vitrectomy and lens repositioning or lens exchange.

PURPOSE: To compare the visual results and the postoperative complications in eyes with posterior chamber intraocular lens (PCIOL) dislocation that underwent pars plana vitrectomy with lens repositioning with eyes that underwent pars plana vitrectomy with lens exchange. DESIGN: Nonrandomized consecutive comparative case series. PARTICIPANTS: Fifty-nine eyes (27 right eyes and 32 left eyes) of 56 subjects (28 women and 28 men) ranging in age from 59 to 90 years. Mean follow-up was 34 months. METHODS: A comparison of the best-corrected preoperative visual acuities, final visual acuities, and postoperative complications in subjects with dislocated PCIOLs that underwent pars plana vitrectomy. Logarithm of the minimum angle of resolution (LogMAR)-converted visual acuities were used for comparison. Categorical data were analyzed by Fisher's exact test, and population means were compared by a pooled Student's t test. MAIN OUTCOME MEASURES: Final mean visual acuities, change in mean visual acuities, and postoperative complications. RESULTS: For all 59 eyes the mean preoperative visual acuity was 20/152, and the mean final visual acuity was 20/48. Final visual results were similar between the eyes that underwent lens repositioning (20/55) and the eyes that underwent lens exchange (20/43; P = 0.19). Final visual results were also similar between the eyes that underwent lens exchange with sutured PCIOL placement (20/51) and the eyes that underwent lens exchange with anterior chamber intraocular lens (ACIOL) placement (20/38; P = 0.26). Final mean visual acuity in eyes that received an ACIOL (20/38) was better than in eyes that underwent repositioning of the dislocated lens into the ciliary sulcus (20/65; P = 0.01). The mean increase in visual acuities was greater for eyes with ACIOL placement compared with eyes with sutured PCIOL placement (P = 0.01). For all eyes, final visual results were unaffected by a concurrent diagnosis of age-related macular degeneration (20/52; P: = 0.71), glaucoma (20/48; P = 0.95), or postoperative cystoid macular edema (20/55; P = 0.45). Final visual acuities were significantly worse in eyes with a detectable preoperative afferent pupillary defect (20/200; P<0.0001). Postoperative retinal detachments developed in 4 of 29 eyes (14%) that underwent lens repositioning and in 2 of 30 eyes (7%) that had lens exchange (P = 0.42). Postoperative lens subluxations occurred in 6 of 29 eyes (21%) that underwent lens repositioning and in 1 of 30 eyes (3%) that underwent lens exchange (P = 0.05). CONCLUSIONS: The final visual results in eyes with dislocated PCIOLs that underwent pars plana vitrectomy with lens repositioning were similar to the visual results obtained in eyes that underwent pars plana vitrectomy with lens exchange. For eyes that underwent lens exchange, final visual results in eyes that received an ACIOL were similar to the visual results obtained in eyes that received a PCIOL; however, eyes with an ACIOL showed a greater increase in mean visual acuity. Eyes with a preoperative afferent pupillary defect had worse final visual results.