VITRECTOMY WITH INTERNAL LIMITING MEMBRANE PEELING FOR TRACTIONAL AND NONTRACTIONAL DIABETIC MACULAR EDEMA: Long-term Results of a Comparative Study.

PURPOSE: To compare the long-term outcomes of vitreomacular surgery in eyes with nontractional diabetic macular edema (DME) with those from eyes with tractional DME. METHODS: Retrospective comparative study from 55 consecutive patients (73 eyes). Twenty eyes were operated on for tractional DME and 53 eyes for nontractional DME unresponsive to laser photocoagulation or triamcinolone intravitreal injections. The best-corrected visual acuity, the central macular thickness, and the surgical complications were analyzed. RESULTS: The mean follow-up duration was 5.3 ± 2.4 years for the group with traction and 4.4 ± 1.7 years for the group without traction (P = 0.13). At 3 years, the mean logarithm of the minimum angle of resolution best-corrected visual acuity had improved significantly from 0.78 to 0.58 for the group without traction and from 0.75 to 0.45 for the group with traction (P < 0.001). At the final visit, there was no significant difference between the 2 groups in regard to visual or central macular thickness improvement (P = 0.447 and P = 0.742, respectively). The incidence of surgical complications was not significant between the two groups. The preoperative best-corrected visual acuity was the only predictive factor for the final best-corrected visual acuity. CONCLUSION: The results of vitrectomy were not different in terms of anatomical and visual outcomes and surgical complications between eyes without tractional DME and eyes with tractional DME.

Epiretinal membrane recurrence: incidence, characteristics, evolution, and preventive and risk factors.

BACKGROUND: To evaluate the incidence, evolution, clinical characteristics, possible risk factors or preventive factors, and visual outcomes of epiretinal membrane (ERM) recurrence. METHODS: Retrospective study of 440 consecutive patients (440 eyes) who underwent pars plana vitrectomy for ERM. The internal limiting membrane (ILM) was peeled in 266 cases, with the help of indocyanine green in 27 cases and brilliant blue in 45 cases. Cases of symptomatic ERM recurrence were reoperated. RESULTS: The incidence of ERM recurrence was 5% (22/440), and 2% of the patients were reoperated (9/440). Epiretinal membrane recurrence was symptomatic in 9 cases (41%) and asymptomatic in 13 cases (59%). ILM peeling was the only factor preventing ERM recurrence (adjusted odds ratio = 0.33, P = 0.026). The use of staining dyes did not prevent recurrence (adjusted odds ratio = 0.35, P = 0.338). In the case of ERM reproliferation, the absence of ILM peeling, the existence of ERM on the fellow eye, and poor visual acuity before surgery seemed to be associated with a high risk of symptomatic recurrence and reoperation. The mean duration for follow-up was 3.5 ± 1.7 years. CONCLUSION: ILM peeling not only reduces the likelihood of reproliferation of ERM but also seems to improve the visual prognosis of recurrent ERMs. The use of dyes did not reduce the rate of recurrence compared with when ILM was peeled without dyes.

Paracentral retinal holes occurring after macular surgery: incidence, clinical features, and evolution.

AIM: To describe the incidence, clinical features, and evolution of paracentral retinal holes occurring after macular surgery. METHODS: A retrospective non-randomized study of 909 patients operated on for either a macular hole (MH, n = 400 patients) or an epiretinal membrane (ERM, n = 509 patients) between 2004 and 2009. Six patients (0.6%) developed a paracentral macular hole after surgery. Their clinical, auto-fluorescence, and optical coherence tomography (OCT) characteristics as well as their visual outcomes were studied. RESULTS: The mean age of patients was 70 years. Paracentral holes occurred approximately 5 weeks after surgery (with a range of 2-12 weeks). All patients were asymptomatic. Five patients underwent ILM peeling during initial surgery. Paracentral retinal holes were located superiorly to the fovea in three cases and temporally in the other three cases. Mean pre-operative BCVA was 20/200 and mean post-operative BCVA was 20/40. The eye where the eccentric MHs were closest to the fovea (inferior to 1 optic disc area) had the poorest final visual acuity. Autofluorescence imaging showed a bright fluorescence in paramacular holes. On OCT images, they were shown to be flat full-thickness holes. No treatment was attempted. No rhegmatogenous complications or choroidal neovascularization occurred in any of the patients. Mean follow-up was 2 years. CONCLUSIONS: In summary, paracentral MHs are uncommon complications which can occur at the site where ILM peeling has been initiated or completed. Except for the closest holes to fovea, they have good visual prognosis and do not require any treatment underlining the importance of initiating the ILM peeling as far as possible from the fovea.

25-, 23-, and 20-gauge vitrectomy in epiretinal membrane surgery: a comparative study of 553 cases.

PURPOSE: To compare the safety and functional outcomes of 25-gauge and 23-gauge (G) micro-incision vitrectomy surgery (MIVS) instrumentation with the standard 20-G vitrectomy system in the treatment of epiretinal membranes (ERM). METHODS: A retrospective comparative study of 553 consecutive cases with epiretinal membrane who underwent pars plana vitrectomy. Twenty-gauge, 25-gauge and 23-gauge vitrectomy was performed respectively in 347, 91, and 115 eyes. Surgery duration, visual acuity improvement, intraocular pressure variation, intraoperative and postoperative complications were analyzed. RESULTS: The mean surgical time in the 23-G group and in the 25-G group was shorter than in the 20-G group (P < 0.001). Visual improvement was higher 8 days postoperatively in the 25-G group than in the 20-G and 23-G groups (P = 0.035), but not at 6 weeks postoperatively (P = 0.186). In the 20-G group, the IOP increased significantly on the first day postoperatively (P < 0.001), while in the 23-G group, the IOP decreased on the first day postoperatively (P = 0.073). In the 25-G group, the IOP did not change significantly (P = 0.807). The incidence of complications was not statistically significant between the three groups. Retinal breaks were significantly related to the induction of posterior vitreous detachment, independent of the system gauge. CONCLUSION: In ERM surgery, 23-G and 25-G (MIVS) systems are as safe and effective as the 20-G system, and significantly reduce surgical time. Although the 25-G system provides an earlier visual improvement, the 23- and 25- gauge systems are comparable, and the selection will depend on the surgeon's preference.

Cytomegalovirus retinitis associated with Good's syndrome.

PURPOSE: To report a case of cytomegalovirus (CMV) retinitis associated with Good's syndrome. METHODS: A 57-year-old man presented to our ophthalmology clinic with complaints of visual loss in the left eye for 2 weeks. His medical anamnesis revealed myasthenia gravis, thymoma resection, multiple chest infections, and Campylobacter septicemia. Left eye examination revealed mild anterior uveitis, moderate vitritis, and superotemporal active retinitis. RESULTS: Polymerase chain reaction of both aqueous humor and vitreous tap were positive for CMV DNA, which suggested CMV retinitis. The patient was treated with systemic treatment of acyclovir and ganciclovir combined with weekly intravitreal injections of ganciclovir and foscarnet. Retinitis resolved within 3 weeks and visual acuity improved. CONCLUSIONS: CMV retinitis can be associated with Good's syndrome.

Retinitis Pigmentosa and Other Dystrophies.

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerations characterized by progressive degeneration of rod and cone cells that affects predominantly peripheral visual fields. Macular edema may cause additional central visual acuity decrease. Cystoid macular edema (CME) is one of the few treatable causes of visual loss in RP. The prevalence of CME in RP has been found to be between 10 and 20% on fluorescein angiography-based studies, and as high as 49% on reports based on optical coherence tomography. Macular edema can manifest at any stage of the disease and may be unilateral or bilateral. It can be found in any genetic form, but is more often associated with RP caused by CRB1 mutations. The origin of macular edema in RP patients still remains poorly understood. Some mechanisms have been suggested, including antiretinal antibodies (retinal, carbonic anhydrase, and enolase antibodies), vitreous traction, retinal pigment epithelium dysfunction, and Müller cell edema. There is no gold standard therapeutic strategy. Drug therapy is the primary treatment. Systemic carbonic anhydrase inhibitors, such as oral acetazolamide or topical dorzolamide, are still the mainstays of initial therapy. If CME is refractory to acetazolamide, intravitreal corticosteroid injections may be a therapeutic option. However, antivascular endothelium growth factor injections have limited effect and should be avoided. Vitrectomy has also been evaluated, but its exact role remains to be determined. The benefits of these therapies are variable among patients. The establishment of therapeutic approaches is limited by our poor understanding of the pathophysiology of CME in patients with RP. Autoimmune retinopathies (AIRs) are a group of rare diseases characterized by acute or subacute progressive vision loss and are thought to be mediated by autoantibodies specific to retinal antigens. The AIRs encompass paraneoplastic syndromes, such as cancer-associated retinopathy and melanoma-associated retinopathy, and a larger group of AIRs that have similar clinical and immunological findings but without underlying malignancy. These diseases may also be complicated by macular edema. RP is one of the most common forms of inherited retinal degeneration. It displays extensive clinical and genetic variations and leads to progressive blindness with variable onset.

Cone dysfunction as a paraneoplastic syndrome associated with retinal antigens approximating 40 kiloDalton.

Reports on cancer-associated retinopathies (CAR) have increased in recent years as the autoimmune reactions responsible have become better understood. The 23-kDalton autoantigen 'recoverin' was the first retinal antigen implicated in CAR, but others have since been described. We report an additional case involving an autoantigen other than recoverin, with five-year follow-up of a 50-year-old woman suffering from the CAR syndrome, with ocular abnormalities restricted to cone dysfunction. The patient had a history of laryngeal carcinoma surgically removed 18 months prior to presenting to the ophthalmologist with photophobia and decreased vision in both eyes. The patient's abnormal retinal hypersensitivity included antibody activity with two retinal antigens approximating 40 kD, located within the outer segments of the photoreceptor layer. To our knowledge, this is the first description of a cancer-associated, cone-specific dystrophy involving an abnormal amount of immunologic activity with two retinal proteins approximating 40 kD, that may prove to be isoforms of the same antigen.

Prosaposin gene expression in normal and dystrophic RCS rat retina.

PURPOSE: To identify proteins secreted by the retinal pigment epithelium (RPE) and to analyze their cellular distribution in normal and pathologic rat retinas at various stages of eye development. METHODS: A cDNA library was constructed with RNA isolated from porcine RPE sheets and screened by using the yeast signal sequence trap system. In situ hybridization, immunohistochemistry, and semiquantitative RT-PCR analysis were performed on rat retinas. RESULTS: The cDNA encoding prosaposin was isolated. This is the first time this gene has been shown to be expressed in the retina. Prosaposin mRNA was detected in the rat RPE cell monolayer and in ganglion cells 14, 21, and 45 days after birth. The amount of prosaposin mRNA increased between days 14 and 45 after birth in normal retinas (rdy+), but not in the pathologic retinas (rdy-) of RCS rats. CONCLUSIONS: Several techniques were used to determine the localization of prosaposin in rat retinas. The increase in the amount of prosaposin mRNA in normal retinas coincided with the maturation of photoreceptor cells and the beginning of the phagocytosis process. In addition, the RCS rdy- RPE cells, characterized by the abrogation of the ingestion phase of the photoreceptor outer segments, are deficient in prosaposin expression.

The aging of the retina.

This mini-review summarizes our current knowledge concerning the age-related changes that affect the retina. Over the last 10 years, our understanding of the genetics of hereditary retinal diseases has improved considerably. However, the modifications that occur in the retina as a result of aging are still under investigation. In this review, we place particular emphasis on the normal retinal alterations that occur with aging (gene modulation; psychophysical, structural and cellular alterations). We describe the events that occur during the pathological aging process, such as in age-related macular degeneration. Understanding these different modifications is essential if we are to find key players on which to base therapeutic interventions that may help to prevent the passage of normal aging process to the pathological aging process.

[Amniotic membrane transplantation for the treatment severe acanthamoeba keratitis]. / Intérêt de la greffe de membrane amniotique dans le traitement des kératites amibiennes sévères.

BACKGROUND: It is now possible to treat ocular surface disorders by means of amniotic membrane transplantation. We performed a study to determine the efficacy of this technique in the treatment of severe Acanthamoeba keratitis. METHODS: We studied six patients with severe, painful, nonhealing Acanthamoeba keratitis who underwent one or two amniotic membrane transplantation procedures between February 2001 and January 2003. Histopathological analysis of the corneal buttons was performed in four cases. RESULTS: Eight amniotic membrane transplantation procedures were performed. The mean length of follow-up was 14 (range 3-21) months. The mean interval between institution of medical treatment and the procedure was 3.6 months. All patients had progressive stromal lesions caused by an inflammatory reaction. Complete reepithelialization occurred in four cases, and partial healing in two cases. Ocular inflammation and tissue destruction were decreased in all cases, pain was lessened in five cases, and corneal neovascularization was decreased in four cases. No postoperative complications were observed. Amniotic membrane was observed under dysplastic corneal epithelium on histologic examination. INTERPRETATION: Amniotic membrane transplantation may be a safe and effective treatment of severe Acanthamoeba keratitis, particularly during the inflammation phase. It may permit penetrating keratoplasty to be delayed.

Epiretinal membrane surgery outcomes in highly myopic eyes without traction maculopathy: long-term results of a case-control study.

PURPOSE: To evaluate the outcomes of epiretinal membrane (ERM) surgery in highly myopic eyes without traction maculopathy, and to compare them with those from non-highly myopic eyes. DESIGN: Retrospective nested case-control study from a cohort of 509 consecutive patients (509 eyes) who underwent pars plana vitrectomy with ERM removal. METHODS: Thirty-two highly myopic eyes (with a refractive error of more than -6.00 diopters [D]), which underwent surgery for isolated ERM, were included in the study. For each case studied, we selected from the same cohort 2 age-matched controls who had ERM surgery (n = 64 non-highly myopic eyes). The best-corrected visual acuity (BCVA), the central macular thickness (CMT), and the surgical complications were analyzed. RESULTS: The mean follow-up duration was 3.2 ± 1.5 years for the study cases and 3.4 ± 1.6 years for the control group (P = .608). At the final follow-up examination, the mean logMAR BCVA had improved significantly, from 0.56 to 0.26 (P < .001) for the case group and from 0.54 to 0.22 (P < .001) for the control group. At the final optical coherence tomography (OCT), the mean CMT had improved significantly, from 433 to 314 µm (P < .001) for the case group and from 428 to 303 µm (P < .001) for the control group. There was no significant difference between the 2 groups as regards visual or CMT improvement (P = .526 and P = .483, respectively). The incidence of surgical complications was not significant between the 2 groups. CONCLUSIONS: The results of ERM surgery were not different in terms of anatomic and visual outcomes and surgical complication between highly myopic and non-highly myopic eyes.

Retinitis pigmentosa and other dystrophies.

Retinitis pigmentosa (RP) is an inherited retinal degeneration that affects predominantly peripheral visual fields. Macular edema may cause additional central visual acuity decrease. Fluorescein angiography and/or optical coherence tomography detect the presence of macular edema in 10-20% of RP patients. Macular edema can manifest at any stage of the disease and may be unilateral or bilateral. In X-linked forms, macular edema is very rare. The origin of macular edema in RP patients still remains poorly understood. The possible pathophysiological role of autoantibodies has been suggested (retinal, carbonic anhydrase, and enolase antibodies). Drug therapy is the primary treatment for macular edema in patients with R P. Systemic carbonic anhydrase inhibitors, such as oral acetazolamide or topical dorzolamide, still are the mainstay of initial therapy. If cystoid macular edema is refractory to acetazolamide, intravitreal corticosteroid injections could be administered. Intravitreal anti-vascular endothelial growth factor therapy has also been used in cases of macular edema persistence after oral acetazolamide therapy, though with uncertain results. Vitrectomy can also be proposed, but its role is not clear yet. Autoimmune retinopathies (AIRs) are a group of rare diseases characterized by acute or subacute progressive vision loss and are thought to be mediated by autoantibodies specific to retinal antigens. The AIRs encompass paraneoplastic syndromes, such as cancer-associated retinopathy and melanoma-associated retinopathy, and a larger group of AIRs that have similar clinical and immunological findings but without underlying malignancy. These diseases may also be complicated by macular edema.

Retinal cell type expression specificity of HIV-1-derived gene transfer vectors upon subretinal injection in the adult rat: influence of pseudotyping and promoter.

BACKGROUND: Gene therapy, and particularly gene restoration, is currently a great hope for non-curable hereditary retinal degeneration. Clinical applications require a gene transfer vector capable of accurately targeting particular cell types in the retina. To develop such a vector, we compared the expression of a reporter gene after subretinal injections of lentiviral constructs of various pseudotypes and with the transgene expression driven by various promoters. METHODS: Lentiviral vectors expressing the green fluorescent protein (GFP) under the transcriptional control of cytomegalovirus (CMV), mouse phosphoglycerate kinase (PGK), human elongation factor 1-alpha (EF1alpha), or human rhodopsin (RHO) promoters were pseudotyped by vesicular stomatitis virus (VSV) or Mokola virus envelope proteins. These constructs were injected into the subretinal space of adult rdy rats. GFP expression was analyzed in vivo 1 and 4 weeks after injection by fundus examination. The precise location of transgene expression was then determined by immunohistochemistry and in situ hybridization. RESULTS: Constructs of both vesicular stomatitis virus and Mokola pseudotypes with ubiquitous promoters led to a strong expression of GFP in vivo. Histological studies confirmed the production of GFP in the retinal pigment epithelium (RPE) in most cases. However, only the combination of the VSV pseudotype with the RHO promoter led to GFP production in photoreceptors, and did so in a sporadic manner. CONCLUSIONS: Mokola-pseudotyped lentiviral vectors are effective for specific gene transfer to the RPE. Neither VSV- nor Mokola-pseudotyped lentiviral vectors are adequate for efficient gene transfer to photoreceptors of adult rats.