[The IC3D classification of the corneal dystrophies]. / IC3D-Klassifikation von Hornhautdystrophien.

BACKGROUND: The recent availability of genetic analyses has demonstrated the shortcomings of the current phenotypic method of corneal dystrophy classification. Abnormalities in different genes can cause a single phenotype, whereas different defects in a single gene can cause different phenotypes. Some disorders termed corneal dystrophies do not appear to have a genetic basis. PURPOSE: The purpose of this study was to develop a new classification system for corneal dystrophies, integrating up-to-date information on phenotypic description, pathologic examination, and genetic analysis. METHODS: The International Committee for Classification of Corneal Dystrophies (IC3D) was created to devise a current and accurate nomenclature. RESULTS: This anatomic classification continues to organize dystrophies according to the level chiefly affected. Each dystrophy has a template summarizing genetic, clinical, and pathologic information. A category number from 1 through 4 is assigned, reflecting the level of evidence supporting the existence of a given dystrophy. The most defined dystrophies belong to category 1 (a well-defined corneal dystrophy in which a gene has been mapped and identified and specific mutations are known) and the least defined belong to category 4 (a suspected dystrophy where the clinical and genetic evidence is not yet convincing). The nomenclature may be updated over time as new information regarding the dystrophies becomes available. CONCLUSIONS: The IC3D Classification of Corneal Dystrophies is a new classification system that incorporates many aspects of the traditional definitions of corneal dystrophies with new genetic, clinical, and pathologic information. Standardized templates provide key information that includes a level of evidence for there being a corneal dystrophy. The system is user-friendly and upgradeable and can be retrieved on the website www.corneasociety.org/ic3d .

Multicenter trial of acyclovir and trifluorothymidine in herpetic keratitis.

Acyclovir 3 percent ophthalmic ointment was compared with trifluorothymidine 2 percent ointment in a double-blind trial of 59 herpes keratitis patients. Clinical progress was measured by direct clinical assessment and retrospective photographic evaluation. Ninety percent of acyclovir-treated patients and 75 percent of trifluorothymidine-treated patients had healed within 14 days. There was no significant difference in the rate of healing between the two treatment groups.

Influx of immunoglobulins from the vascular compartment into a grafted cornea.

PURPOSE: To determine the effect of a fresh corneal wound or a healed corneal scar on the immunodiffusion of immunoglobulins into the cornea. METHODS: F344 rats were immunized with human serum albumin (HSA) 1 week before an autologous rotational keratoplasty of the right cornea or 1 year after an autograft was performed. One group of rats also was treated with gentamicin-dexamethasone ointment in the grafted eye for 1 week after transplantation to reduce the postsurgical inflammatory signs. A serum sample was drawn every week and booster injections with HSA were given after 2 and 3 weeks. At various times after immunization, groups of rats were killed, blood and aqueous humor samples were taken, and the corneas of both eyes were removed. The corneas were divided into the graft or a 3-mm central button and the peripheral rim and weighed. The anti-HSA titer was determined in serum, aqueous humor, and both parts of the corneas. RESULTS: Up to 5 weeks after transplantation, the grafted cornea contained more anti-HSA immunoglobulins than did the control eye. One year postgrafting, no difference was seen. In the first weeks after keratoplasty, influx of anti-HSA from the peripheral into the central cornea was, however, neither obstructed nor enhanced. CONCLUSIONS: Surgical trauma in itself causes increased influx of anti-HSA immunoglobulins into the cornea. Within the cornea, a wound or a scar does not appear to be a barrier for centripetal immunoglobulin diffusion.

Prevention of corneal allograft rejection in rats treated with subconjunctival injections of liposomes containing dichloromethylene diphosphonate.

PURPOSE: The drug dichloromethylene diphosphonate (CL2MDP) encapsulated in liposomes depletes macrophages but not other immunocompetent cells. The authors investigated whether subconjunctival injection of CL2MDP containing liposomes (CL2MDP-LIP) could prolong survival of corneal allografts in rats. METHODS: Male Fisher rats received orthotopic corneal grafts of Dark Agouti origin. Rats were treated postoperatively with subconjunctival injections of 0.1 ml CL2MDP-LIP at the time of transplantation and on days 2, 4, 6, and 8 after transplantation. Control groups received either liposomes containing phosphate-buffered saline subconjunctivally at the same time points or no additional treatment. Corneal grafts were evaluated every other day and were scored for neovascularization, opacity, and edema. Immunohistologic evaluation was performed 12 and 19 days after surgery. RESULTS: Corneal grafts in both control groups were rejected within 17 days. In the Cl2MDP-LIP treated rats, grafts were not rejected during the maximum follow-up of 100 days. Cellular infiltration in these grafts was clearly reduced. There was also a strong reduction in neovascularization of the cornea. CONCLUSIONS: Rejection of orthotopic allogeneic corneal grafts could be prevented by repeated subconjunctival injection of Cl2MDP-LIP.

Effect of macrophage depletion on immune effector mechanisms during corneal allograft rejection in rats.

PURPOSE: In rats, corneal allograft rejection is delayed for at least 100 days by clodronate liposomes. These liposomes selectively deplete macrophages. To investigate the immunologic basis for absence of graft rejection in treated rats, the effect of these liposomes on the generation of cytotoxic T lymphocytes (CTLs) and antibody production after orthotopic corneal allotransplantation was determined. METHODS: Transplantations of corneal buttons from PVG rats were performed in AO rats. After surgery, one group received clodronate liposomes subconjunctivally at five time points, and the other group remained untreated. On postoperative day (POD) 3, 7, 12, or 17, rats were killed, the presence of CTLs was investigated at three different anatomic locations, and antibodies against donor antigens were tested. RESULTS: No significant differences were found between the groups tested 3 and 7 days after surgery. But on POD 12 (the time of onset of rejection in the untreated group) and on POD 17, the CTL activities detected in the submandibular lymph nodes (P < or = 0.008) and the spleen (P < or = 0.009) were significantly less in the treated groups compared with the untreated groups. In the untreated groups complement-independent antibodies were present only on POD 17, whereas no antibodies were found in the treated rats. CONCLUSIONS: Local treatment with clodronate liposomes was shown to downregulate local and systemic CTL responses and to prevent the generation of antibodies. Local depletion of macrophages in the initiation phase of the immune response appears to lead to a less vigorous attack on the grafted tissue and therefore to promote graft survival.

Configuration of corneal trephine opening using five different trephines in human donor eyes.

In this laboratory study, we used five different corneal trephines on 60 fresh human donor eyes with controlled intraocular pressure to study the variation in the size and shape of the trephine openings. With all trephines, the average diameter of the button was larger than the diameter of the trephine at the epithelial side (mean difference, 0.21 mm; range, 0.06 to 0.35 mm) and the endothelial side (mean difference, 0.42 mm; range, 0.13 to 0.79 mm), presumably because the corneal tissue protruded into the trephine during cutting. The trephines that produced the most uniform opening were a nondisposable suction trephine and a freestanding disposable blade, but they caused some undercutting.

Clinical comparison of grafts stored in McCarey-Kaufman medium at 4 degrees C and in corneal organ culture at 31 degrees C.

Twenty-eight paired human corneas were preserved in minimal essential medium at 31 degrees C and in McCarey-Kaufman medium at 4 degrees C. These grafts were then transplanted in pairs of patients with keratoconus who were age matched as closely as possible. These pairs received donor corneas from the same donor, so for each pair the donor age and time from death to preservation were the same. Visual acuity, central corneal thickness, and endothelial cell counts were compared. During the 1- to 2-year study period, no statistically significant difference in visual acuity, corneal thickness, or endothelial cell density was found between grafts stored in minimal essential medium and those stored in McCarey-Kaufman medium.

Refractive predictability of myopic hydrogel intracorneal lenses in nonhuman primate eyes.

The refractive predictability of myopic hydrogel intracorneal lenses made of lidofilcon A was evaluated in 24 monkey eyes following a microkeratome dissection. All eyes were examined monthly for refractive alteration and clinical appearance during a follow-up period of 7 to 33 months. The refractive yield was measured by retinoscopy and found to be a function of the implant depth. The mean +/- SD percent of the desired correction achieved averaged 70% +/- 24% at a 36% to 60% depth (n = 8), 54% +/- 22% at a 61% to 79% depth (n = 7), and 12% +/- 14% in implants deeper than at a 79% depth (n = 9). For eyes with implants at a 36% to 60% depth, the predicted vs achieved refractive alteration yielded a correlation coefficient of .97 (88% within +/- 3 diopters of the correlation). The refractive outcome remained stable throughout 7 months of follow-up, whereas deeply placed lenses (greater than or equal to 80%) exhibited significant regression in power during this time.

Complications of hydrogel intracorneal lenses in monkeys.

We performed 32 hydrogel keratophakia procedures in rhesus monkey corneas. Surgery was technically successful in 20 eyes. Toxic stromal keratitis occurred in five eyes because of impurities on the lenticules. Fibrosis appeared around the implant in five eyes. Two eyes showed aseptic necrosis of the inferior cornea with extrusion of the implant, attributed to exposure keratitis. Complications during surgery included faulty microkeratome incisions (three eyes) and epithelial implantation in the lamellar bed (one eye). Three lenticules decentered, one extruding through the wound, probably because the monkeys rubbed their eyes excessively. Nine of the 11 eyes with postoperative refraction data showed overcorrection or undercorrection of more than 1.00 diopter. Most of these complications could have been prevented by better technique, design, and manufacture of the lenticule or cooperation of the subjects.

Refractive results of hyperopic hydrogel intracorneal lenses in primate eyes.

Hyperopic hydrogel intracorneal lenses were successfully implanted into 27 of 33 primate eyes. All eyes were evaluated preoperatively and postoperatively at monthly intervals for clinical appearance and refractive alteration. In a preliminary surgical series, several factors, such as tight sutures and implant design, resulted in a poor refractive yield. The final surgical series used a microkeratome with a pediatric microkeratome ring for smooth interface cuts, interrupted suturing with sufficient tension to align the wound without compression, a suture through the lens to prevent its dislocation, and intraoperative keratometry to reduce postoperative cylinder. The predicted vs measured refractive alteration for a range of 6 to 20 diopters had a correlation coefficient of .95. Keratometry changes correlated to the refractive changes with a coefficient of .97 but understand the change in refraction created by the surgery.

Hydrogel intracorneal lenses in aphakic eyes.

BACKGROUND: The theoretical benefits of synthetic keratophakia over conventional corneal lamellar procedures are the elimination of donor concerns and superior refractive predictability. Additionally, synthetic material can be inspected for optical quality and power, and it can be sterilized. Furthermore, visual recovery should be more rapid since epithelium is not removed from the central part of the cornea and the need for keratocyte repopulation is eliminated. OBJECTIVE: To present results on patients who received an intracorneal implant (Kerato-Gel, Allergan Medical Optics, Irvine, Calif) that was made from lidofilcon A, a glucose-permeable hydrogel with an equilibrium water content of 68%. METHODS: The intracorneal implants were implanted in 35 adult patients for correction of aphakia. Inclusion criteria excluded patients with aphakia who were candidates for intraocular lenses. RESULTS: A total of 19 patients were followed up through 2 years postoperatively. For 16 patients with 2-year postoperative refractive data, the average spherical equivalent was -0.63 +/- 2.07 diopters (D). At 2 years, 88% of patients were within +/- 3.00 D of plano and 50% were within +/- 1.00 D. the mean change in Snellen's line for corrected visual acuity was -3.25 lines at 2 years for all patients and -2.0 lines for a subgroup of five patients who were free of vision-limiting preoperative disease. CONCLUSIONS: Results suggest that this intracorneal implant is well tolerated by the cornea and can provide predictable refractive results in patients with high-risk aphakia. Limitations of the procedure are uneven microkeratome resections, loss of best-corrected visual acuity, and irregular astigmatism in some patients. Although these data show good evidence of biocompatibility of the implant material, technical surgical progress is needed to advance this procedure into clinical therapeutic practice.

Use of passive function testing in venous insufficiency: a prospective study.

In a prospective study, the results of venous function tests in 19 lower extremities with deep venous insufficiency and in seven control extremities were compared. First, the routine method of asking the patients to exercise their calves was used. Second, cuffs around the calves were rapidly inflated, producing standardized external compression to the calf muscle pump. Our aim was to decrease the influence of artifacts from involuntary muscle efforts and especially to render reproducible results of pressure reduction after passively pumping. The passive function test proved to be the only technique with which a decrease in pressure measured with strain gauges while the patient was in the standing position could significantly be discriminated between diseased and control extremities. Furthermore, the correlation of pressure decrease invasively versus measured noninvasively improved to 37% and thus became significant. Simulating calf venous pump function with the aid of inflatable cuffs is easily applicable in the vascular laboratory. It enables the vascular surgeon to reliably quantify venous recovery time and pressure reduction.

Endoluminal pulse oximetry in ischemic colon in a swine model.

BACKGROUND: Postoperative sigmoidal ischemia after aortic grafting is a severe complication. No simple methods are available to detect this entity at an early stage. This study was done to monitor for sigmoidal ischemia with a new endoluminal probe based on pulse oximetry (SmO2). STUDY DESIGN: A prospective controlled animal study was done. Five pigs with low flow in the caudal mesenteric artery (20 percent of the basal flow) and four pigs in a control group were included. General and local circulatory parameters were monitored in the carotid and pulmonary artery and in the caudal mesenteric vein (CMV). Mucosal biopsy specimens were taken for histologic examination. Statistical analysis was done with the Wilcoxon and Mann-Whitney rank sum test and with analysis of variance. RESULTS: During the first two hours of ischemia, no sigmoidal pulse was detected. During the third hour, in three pigs the pulse curve reappeared with a SmO2 of 48 to 88 percent. After two hours, the mean oxygen saturation in the CMV of the ischemic group was 64 percent (compared with the control group, 77 percent, p < 0.05). After one hour, the mean lactate concentrations were 2.0 and 1.3 mmol per L, respectively (p < 0.05). Significant histologic changes occurred with neutrophilic infiltration in the crypts, in the lamina propria, and in the submucosa. CONCLUSIONS: Low-flow sigmoidal ischemia can be detected and monitored with endoluminal pulse oximetry in this model of early sigmoidal ischemia.

Changes in corneal curvature induced by sutures and incisions.

To clarify the mechanisms by which incisions and sutures produce corneal astigmatism, we made incisions and wedge resections closed by sutures in the corneoscleral limbus of human eye bank eyes, studying the changes in corneal curvature by shadowgraph photography of the corneal contour, by central keratometry, and by measurement of corneal diameter. The compression of tissue within the sutures or the closure of an excision of a wedge of tissue by sutures induced astigmatism in the meridian of surgery regardless of changes in the sagittal depth of the anterior chamber. Sutures and wedge resections closed by sutures in the anterior part of the cornea compressed or removed more tissue from the anterior part than the posterior part, producing a depression of the limbal cornea toward the anterior chamber and steepening the central cornea in the meridian of surgery. The corneal diameter decreased in that meridian. In the opposite meridian, the cornea flattened, the corneal diameter increased, and the sagittal depth decreased.

Postoperative astigmatism after central vs eccentric penetrating keratoplasties.

Six patients with markedly eccentric penetrating keratoplasties had severe corneal astigmatism (mean, 10.38 +/- 2.91 diopters). In four of these patients the flat meridian was lying in the direction of graft displacement. Laboratory experiments disclosed no statistically significant difference in diameter between the major and minor axes of the corneal buttons in the centrally and eccentrically trephined eyes and we could not elucidate the mechanism of the severe astigmatism. However, in the eccentrically trephined eyes the longer axis consistently lay in the direction of decentration whereas in the centrally trephined eyes the long axis was oriented randomly.

Experimental circular keratotomy for correction of corneal astigmatism.

PURPOSE: To investigate the effect of circular keratotomy depth and diameter on corneal astigmatism. METHODS: High astigmatism was induced in 25 human donor eyes by an anterior radial 7-0 silk suture across the corneoscleral limbus. With a 6.0, 6.5, 7.0, or 7.5 mm trephine, a 0.3 mm deep circular incision was made in 20 donor eyes. In 5 donor eyes 5 circular incisions were made with a diamond knife set at 0.1, 0.2, 0.3, 0.4, and 0.5 mm depths. RESULTS: The reduction of astigmatism between the 4 groups in which different trephination diameters were used showed no statistically significant difference (P > .1). The relationship between incision depth and reduction of astigmatism was statistically significant (P < .001). CONCLUSION: Artificially induced corneal astigmatism was reduced by a circular keratotomy in this donor eye model. Deeper incisions showed a greater effect.

Long-term results of correction of high myopia with an iris claw phakic intraocular lens.

PURPOSE: Anterior chamber phakic intraocular lenses (PIOLs) are one of the modalities used to correct high myopia. We report the long-term results of our prospective study on the Artisan 5-mm optic myopia lens. METHODS: We studied 67 eyes of 38 consecutive patients with preoperative myopia ranging from -5.38 to -28.00 D. All patients were operated by one surgeon. Mean follow-up was 35 months (24 months in 67 eyes and 36 months in 61 eyes). RESULTS: In 45 eyes (67.2%), postoperative residual refraction was within +/- 1.00 D of emmetropia. The mean refraction was stable statistically during the entire follow-up period. Mean best spectacle-corrected visual acuity improved from 20/40 to 20/32. Mean endothelial cell loss at 6 months was 5.5% (range, -52.4% to +9.3%), at 12 months, 7.21% (range, -53.2% to +20.1%), at 24 months, 9.1% (range -43.6% to +13.6%), and at 36 months, 10.9% (range, -43.0O% to +11.4%). The majority of eyes had an increase in best spectacle-corrected visual acuity; 5 eyes lost best spectacle-corrected visual acuity. We encountered no major complications. CONCLUSION: Implanting the Artisan 5-mm optic myopia lens in high myopic eyes resulted in a stable and accurate refractive outcome. The apparent progressive corneal endothelial cell loss remains a matter of concern.

Iris-claw phakic intraocular lens for high myopia.

PURPOSE: To evaluate the efficacy, safety, predictability, and stability of implanting a polymethylmethacrylate (PMMA) phakic intraocular lens (PIOL) (the Artisan myopia lens) to correct high myopia. METHODS: An Artisan myopia lens was implanted in 78 consecutive eyes of 49 patients with preoperative myopia that ranged from -6.25 to -28.00 D. Mean patient age was 42.4 years. Mean follow-up was 10.7 months and all patients were followed for at least 6 months; 45 eyes had follow-up of 12 months, and 10 eyes had 24 months. The desired outcome was emmetropia in all eyes except for those eyes with preoperative myopia greater then -23.00 D. RESULTS: Fifty-three eyes (67.9%) had a postoperative refraction at the last follow-up examination within +/-1.00 D of emmetropia, and 39 eyes (50.0%) had a postoperative refraction +/- within 0.50 D of emmetropia. The postoperative refraction remained stable during the entire follow-up period. Mean spectacle-corrected visual acuity improved from 20/32 preoperatively to 20/25 postoperatively. Mean postoperative uncorrected visual acuity was 20/32. There was no significant change in endothelial cell density from baseline. We did not encounter major complications. CONCLUSION: Implantation of the Artisan myopia lens to correct high myopia resulted in a stable and fairly predictable refractive outcome. A significant endothelial cell change was not detected.

Correction of high myopia with the Worst myopia claw intraocular lens.

BACKGROUND: Phakic anterior chamber lenses is one of the modalities used to correct high myopia. We report the initial results of our prospective study on the Worst myopia claw intraocular lens (IOL) that is fixated to the anterior iris. METHODS: We studied 35 eyes in 18 patients with a preoperative myopia ranging from -6.00 to -28.00 diopters (D). The follow up ranged from 6 months (n = 15) to 12 months (n = 20). RESULTS: In 26 (74.3%) eyes, the postoperative spherical equivalent refractive error was within 1.00 D of emmetropia. The mean refraction was stable between 1 to 2 months and 12 months. The mean spectacle-corrected visual acuity improved from 20/50 to 20/40. The straylight measurements did not show a significant increase postoperatively (p = .64). The mean endothelial cell loss was 5.6% (range, +6.3% to -22.6%) at 6 months, and 8.9% (range, +0.77% to -23.5%) at 12 months. We did not encounter major complications. CONCLUSION: Implanting a Worst myopia claw IOL in high myopic eyes resulted in a stable, reasonably accurate refractive outcome. This group of patients will be followed longer because of concern over ocular complications with this technique.

Silicone oil keratopathy: indications for keratoplasty.

A penetrating corneal graft was performed in 12 patients for corneal opacification induced by silicone oil. The patients were all aphakic. They had had vitrectomy and silicone oil injection for complicated retinal detachment, often with periretinal proliferation. The average follow-up time was 13.7 months, during which four out of 11 grafts failed (one case was lost to follow-up). One patient developed severe calcific band keratopathy, and three grafts failed from endothelial decompensation. Changes induced by silicone oil include band keratopathy, thinning, and endothelial damage. The indications for keratoplasty for these corneal changes are discussed.