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PURPOSE: Amniotic membrane transplantation is currently being used as an alternative approach to treat severe corneal surface disorders refractory to medical therapy. The authors report complications of corneal surface disorders after successful amniotic membrane transplantation. METHODS: Case series. RESULTS: Twenty-eight patients with corneal surface disorders due to severe chemical burns, corneal ulceration, or persistent epithelium defects were treated with amniotic membrane transplantation. Four of these patients showed a spontaneous perforation and three patients developed a descemetocele within 6 weeks after the amniotic membrane transplantation. CONCLUSIONS: In this case series, descemetocele and corneal perforation occurred in 25% of the patients after amniotic membrane transplantation. This might be due to the severity of the underlying disease or to the impact of amniotic membrane on corneal fibroblasts and collagenases. The risk of corneal thinning and perforation should be considered in the decision of treatment with amnion and follow-up regimen.

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BACKGROUND: During organ culture, corneas swell and have to be de-swollen prior to transplantation using a medium. Both swelling and de-swelling lead to increased endothelial cell loss. Furthermore, dextran, the standard de-swelling substance, is toxic and deposited in the cornea. Whether HES is suitable as a continuous supplement for organ culture and keeps the corneas thin was investigated in this study. METHODS: Forty-five human corneas were stored in MEM plus 7.5% HES 130 for 7, 15, 21, and 28 days. Endothelial cell count was determined before and after organ culture. After storage the water content and amount of adenosine phosphates were measured. RESULTS: Water content was 82.29% after 7 days, 82.98% after 15 days, 81.15% after 21 days, and 83.21% after 28 days. The endothelial cell count decreased by 1.20% after 7 days, 0.60% after 15 days, 4.29% after 21 days, and 6.89% after 28 days. ATP was 0.159 micromol/g dry weight after 28 days of organ culture. CONCLUSION: The water content of corneas stored in HES-containing medium remained constant even after 21 days of organ culture. Endothelial cell loss was less than in comparable studies using a standard medium containing 10% FCS; however, ATP concentrations were worse. HES 130 keeps the corneas thin and can be used as a continuous supplement. It facilitates the handling of corneas during organ culture, making dehydration before transplantation unnecessary, and thus also reduces potential stress factors for the cornea.

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BACKGROUND: Previously published prospective therapeutic intervention studies in ocular hypertension and glaucoma are summarized. MATERIAL AND METHODS: The concept of intraocular pressure reduction was evaluated in normal tension glaucoma ["Early manifest glaucoma trial (EMGT)"], the "Collaborative normal-tension glaucoma study (CNTGS)" and ocular hypertension ["Ocular hypertensive study (OHTS)" as well as the "European glaucoma prevention study (EGPS)"]. Early open angle glaucoma patients were included in the EMGT trial as well as the "Collaborative initial glaucoma treatment study (CIGTS)", whereas advanced glaucoma patients were examined in the "Advanced glaucoma intervention study (AGIS)". RESULTS: The study design, the results and the conclusions will be highlighted in the text. CONCLUSIONS: The therapeutic concept of intraocular pressure reduction decreases the risk of progression by 50 % in normal tension glaucoma, ocular hypertension and early open angle glaucoma. The mean pressure reduction to 12 mmHg in advanced glaucoma abolished visual field progression. The natural course of the disease documented by the control groups is now known. Sensitive glaucoma progression detection is clinically available by glaucoma change probability maps (Humphrey-full threshold perimetry) used in the EMGT.

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BACKGROUND: Excessively draining fistulas may lead to enucleation when primary suture closure is not effective. In these cases preserved cadaver tissues such as sclera, fascia lata, dura mater and peritoneum have been used for patch graft repair with variable results. In this study, the clinical outcomes after transplantation of scleral patch grafts have been investigated. METHOD: Twenty-eight eyes of twenty-seven patients underwent surgery with homologous scleral patch grafts for repair of excessively draining scleral fistulas after cataract surgery (n = 2), leaking filtering blebs following full-thickness filtration surgery (n = 7), large scleral perforations due to trauma (n = 7), corneo-scleral ulcerations due to severe eye burns (n = 9) or after radiotherapy of malignant melanoma (n = 3). The mean size of the rectangular grafts was 8.6 x 6.7 mm (+/- 2.8/3.1 mm). Clinical follow-up was up to 73 months (median 30 months). RESULTS: Twenty-three of 28 eyes (82.1 %) showed functional closure after initial surgery without any wound complication such as patch retraction or leakage and without evidence of inflammation. In five eyes surgical revision was necessary. Two of these eyes had to be enucleated due to uncontrollable dehiscence after the second operation. Two eyes were enucleated at the patient's demand due to pain. The fifth eye showed effective closure after the second operation. CONCLUSION: In our study scleral patch grafts were useful in adequately closing large corneo-scleral defects in 24 of 28 eyes (85.7 %). The antigen load and, therefore, the rejection of the scleral grafts is minimized due to the denaturation of proteins during the alcohol treatment before storage.

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BACKGROUND: In severe chemical and thermal eye burns the limbal stem cells, which are important for the regeneration of the corneal epithelium, are lost. In our retrospective study two questions were investigated: 1) is it possible to restore the limbal region by transplantation of large diameter keratoplasties 2) has the time of transplantation an influence on the clinical outcome. PATIENTS AND METHOD: In a retrospective study the outcome of 48 eyes (43 patients) with severe chemical and thermal burns were analysed. Large diameter (11 - 12 mm) penetrating keratoplasties were performed between 1987 and 1996. Complete limbal deficiency was present in 17 eyes, while 31 eyes had developed sterile corneal ulceration. According to the time of transplantation three different groups were distinguished. Group I (early keratoplasty, n=24): transplantation within 3 months after the accident (mean: 26 days). Group II (intermediate keratoplasty, n=13): transplantation between 4 - 18 months after the burn (mean: 190 days). Group III (late keratoplasty, n=11): surgery more than 18 months after the injury (mean: 36.6 months). RESULTS: Follow-up time was 28.4 months in early keratoplasty, 26.4 months after intermediate keratoplasty, and 34.3 months in late keratoplasty. Long-term results of the keratoplasties were poor. 60.4 % of the transplants failed due to surface problems, 18.8 % due to endothelial rejection episodes. Late keratoplasties were significantly more successful than intermediate keratoplasties. 25 % of the early keratoplasties and 36.4 % of the late keratoplasties showed an intact limbal region at the end of the follow-up time, but none of intermediate keratoplasties. CONCLUSION: The prognosis for large diameter keratoplasties depends on the time of transplantation. Late and early keratoplasties had the best results. However, survival of heterologous stem cells is limited.

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PURPOSE: To improve the prognosis of corneal grafts in silicone-oil filled eyes of patients with severe ocular trauma by a prolonged application of the Type II Aachen-Keratoprosthesis (KPro). This application endeavors to improve post-keratoplasty prognosis by avoiding corneal endothelial dystrophy in the aphakic eye due to contact with silicone oil. PATIENT AND PROCEDURES: The Aachen-Keratoprosthesis' haptic was modified to allow tight contact with cells. The Type II Aachen-Keratoprosthesis was then implanted in an 18-year-old male, with previous management of bilateral corneal rupture. Rather than utilize the device as a temporary intraoperative tool, we extended the device's lifespan in the eye. MAIN FINDINGS: Following implantation, the patient could see hand movements up to 0.1 with best correction. After 8 weeks, vision decreased and a retroprosthetic membrane proliferated. Upon conjunctival retraction, 3 months after the initial surgery, we excised the prosthesis and performed a re-vitrectomy and corneal grafting. The silicone oil was removed. After eighteen postoperative months, the graft remained clear, the retina was completely attached, and the vision was stable: 0.1 best corrected. CONCLUSION: This case reports the prolonged implantation and prospect of the Type II Aachen-Keratoprosthesis to be utilized as a permanent device to restore vision in the near future.

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Light burns heal well within a few days. Severe chemical and thermal injuries of the eyes destroy surface epithelia and cause ischemic necroses of conjunctiva, cornea, sclera, iris, ciliary body, and lids. An inflammatory response follows with leucocyte infiltration and release of inflammatory mediators. Prostaglandins, lipoxygenase products, cytokines, superoxide radicals and Iysosomal enzymes are known to be active in eye burn disease. Their activities result in corneal, scleral and conjunctival ulceration, tissue proliferation and scarification, which develop within weeks, months and even years after the accident. Pathophysiological events produce defined clinical pictures. Some agents take special actions, e.g. alkali penetrates within seconds into the anterior chamber, sulfuric acid burns as well as quick lime burns forming slaked lime produce considerable heat. Hydrofluoric acid is highly toxic and induces early necroses. Heat causes deep ischemic necroses and lateron strongly shrinking scars. Onset and intensity of first aid decided on the outcome. Immediate rinsing is essential. Cool water, saline, Ringers lactate solution and BSS are good rinsing media. For first aid, buffered Previn seems suitable. Major chemical and thermal injuries need a variety of medical and surgical treatments: Necroses must be excised surgically. Tenon plasty is performed to reconstruct conjunctiva. Amnion-, limbus- and early keratoplasty or artificial epithelium are applied, initially to save the cornea from melting, and later to restore vision. Conjunctical, lid and intraocular surgery may be necessary. The aim of medical treatment is to suppress the inflammatory response and to prevent infection. Corticosteroids, antibiotics, ascorbate and inhibitors of proteolytic enzymes are used. Secondary glaucoma must not be forgotten. Extensive therapy is sometimes rewarding, results are presented.

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Las quemaduras ligeras se curan bien en pocos días. Las quemaduras químicas y térmicas graves de los ojos destruyen el epitelio superficial y causan necrosis isquémica de la conjuntiva, la córnea, la esclera, el iris, el cuerpo ciliar y los párpados. Se produce una respuesta inflamatoria con infiltración de leucocitos y liberación de mediadores inflamatorios. En las enfermedades por quemaduras oculares participan prostaglandinas, productos de lipoxigenasa, citoquinas, radicales superóxido y enzimas lisosomales, cuya actividad produce ulceraciones corneales, esclerales y conjuntivales, proliferación y escarificación de tejidos que se desarrollan en plazos de semanas, meses e incluso años después del accidente. Los eventos patofisiológicos producen cuadros clínicos definidos. Algunos agentes asumen acciones especiales. Por ejemplo, el álcali penetra en segundos en la cámara anterior y las quemaduras de ácido sulfúrico y cal viva producen un calor considerable. El ácido clorhídrico es muy tóxico e induce necrosis tempranas. El calor causa necrosis isquémicas profundas y más adelante cicatrices con un pronunciado encogimiento. La aplicación y la intensidad de los primeros auxilios influyen en el resultado. El lavado inmediato es fundamental. El agua fresca, la solución salina, la solución de lactato de Ringer y BSS son buenos medios de lavado. Para los primeros auxilios, el Previn amortiguado parece adecuado. Las heridas químicas y térmicas grandes requieren una variedad de tratamientos médicos y quirúrgicos: las necrosis deben ser extirpadas con cirugía. Se realizan tenoplastias para reconstruir la conjuntiva. Se aplica amnioplastia, limboplastia y queratoplastia temprana o epitelio artificial, inicialmente para salvar la córnea de la lisis y luego para restablecer la visión. Podría ser necesaria la cirugía conjuntival, del párpado e intraocular. El objetivo del tratamiento médico es suprimir la respuesta inflamatoria y prevenir la infección. Se utilizan corticosteroides, antibióticos, ascorbato e inhibidores de enzimas proteolíticas. No se debe olvidar el glaucoma secundario. La terapia extensiva a veces produce resultados. Se incluyen resultados. (AU)

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BACKGROUND: Late secondary glaucomas after severe chemical or thermal eye burns are associated with diagnostic and surgical difficulties. Routine filtering surgery (trabeculectomy) has a low success rate. In these eyes aqueous shunt implantation and cyclophotocoagulation are alternative procedures. PATIENTS: In our retrospective study, the records of 12 patients with 14 severe eye burns (grade IV) were analyzed. Nine eyes were treated with an aqueous shunt device (six von Denffer and three Ahmed implants). Diode laser cyclophotocoagulation (Iris Medical Instruments) was performed in five eyes. The mean time interval between surgery and accident was 88.3 months (aqueous shunt) and 32.8 months (cyclophotocoagulation). RESULTS: The mean follow-up was 45 +/- 36 months (von Denffer implant), 38 +/- 5 months (Ahmed implant), and 11 +/- 8 months (cyclophotocoagulation). Intraocular pressure (IOP) was reduced from 39 +/- 7 to 23 +/- 6 (von Denffer implants) and from 38 +/- 3 to 8 +/- 10 (Ahmed implants). Mean IOP before treatment with cyclophotocoagulation was 33 +/- 8 and 18 +/- 2 after treatment. Systemic carbonic anhydrase inhibitors were stopped in all patients. Visual acuity deteriorated in five of nine eyes treated with aqueous shunt devices and was unchanged or better in all eyes treated with cyclophotocoagulation. Multiple re-operations were necessary after aqueous shunt implantation. Severe complications leading to failure in these eyes were encapsulated bleb in four eyes, expulsive hemorrhage in one eye, and phthisis in one eye. Cyclophotocoagulation was repeated in two eyes. Severe complications were not observed. CONCLUSION: IOP reduction was effective and comparable in both procedures. Because of the high incidence of severe complications after shunt surgery, we prefer cyclophotocoagulation for the treatment of intractable glaucoma after severe eye burns.

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UNLABELLED: A new keratoprosthesis was used during pars plana vitrectomy in order to test the optical quality, watertightness, short-term biocompatibility and handling of the new device. The implantability was also tested, given that this keratoprosthesis might in future be left in place for several months. This Aachen keratoprosthesis (Aachen-KPro) is developed to be used as permanent implant to restore vision in corneal blind patients. PATIENT AND METHODS: The Aachen-KPro was used during pars plana vitrectomy in 10 patients with opaque corneas. In four cases, trauma precipitated the ocular disease. Eye burn was the cause of corneal and retinal disorders in another four cases. One patient had a history of congenital glaucoma with myopia, and one of uveitis with corneal dystrophy. After trephination of 6.5 mm in diameter, the Aachen-KPro, composed of soft silicone rubber, was temporarily placed in the trephination hole. After completion of the vitrectomy, the Aachen-KPro was replaced by a 7 mm corneal graft. RESULTS: Intraoperative use of the Aachen-KPro allowed uncomplicated intraoperative handling, smooth adaptation to the corneal rim in the trephination hole, and an undistorted view of the central and peripheral retina. Leakage, even during scleral depression, could be avoided by individual suturing of the scleral rim. After a follow-up period of 1-10 months, the retina was still attached in all cases. The corneal graft was clear after surgery in four eyes, and edema was found in three cases. Amnion or conjunctiva was placed over three patients' transplants. CONCLUSION: We report the first temporary implantations of a new keratoprosthesis in 10 patients. Its flexibility and good optical qualities allowed control of intraoperative procedures. The outcome and prognosis of the vitreoretinal surgery and keratoplasty were related to the primary diagnosis. The Aachen-KPro has shown advantages, especially in eyes where the anterior eye segment is severely damaged by eye burn or previous surgical interventions. In the future, prolonged use of the Aa-chen-KPro is planned for selected eyes.

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Adequate treatment of eye burns is an essential task of rescue teams. Clinical and occupational medicine studies have shown that efficient emergency treatment can prevent severe eye damage, but therapy is frequently delayed or inadequate. When initial therapy has been delayed or missed, several treatment strategies, including surgery, are available that may improve the outcome of an injury with poor visual prognosis. Discussed in this review are common accident mechanisms, causative agents and biophysical/pathogenetic aspects of eye burns, together with emergency and long-term treatment strategies including surgical procedures, and factors influencing outcome.

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BACKGROUND: Recent studies have shown that increased intraocular pressure following keratoplasty may cause progressive endothelial cell loss and thereby lead to early transplant failure. This study examined risk groups for development of postoperative glaucoma and thereby transplant failure. MATERIAL AND METHODS: Seventy-five patients with various diagnoses were followed up prospectively for 2, 4, 6, 12, 24, 36, 48, and 60 months. RESULTS: Of the 75 patients 22 showed elevated intraocular pressure after keratoplasty. One-third of these (n = 7) developed a chronic secondary glaucoma. The main risk factor was a preexisting glaucoma (P < 0.05, c2 test), followed by aphakia, especially if aphakia was present before keratoplasty. Three of the six patients with anterior synechia had increased intraocular pressure. Because of the small number of patients neither factors reached statistical significance. CONCLUSION: Intraocular pressure should be closely monitored especially in high-risk patients, although its measurement may not be exact by Schiötz and Goldmann tonometry. Digital impression and controls of the visual field should be carried out additionally.

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PURPOSE: To study metabolic changes of the human cornea during organ-culture. Morphological changes have been extensively studied, whereas changes in human corneal metabolism have not been investigated yet. MATERIAL AND METHODS: 106 human corneas were stored for 1, 7, 15, 18, 21 and 28 days in a closed-system under standard eyebank conditions. After storage, glucose, lactate, ATP, ADP and AMP concentrations were determined in each cornea. RESULTS: Glucose concentration decreased during the first two weeks with a minimum on day 15. ATP and ADP concentrations increased during the same period of time, but had their minimum later, on day 18. Lactate increased during the culture period up to day 21 and decreased thereafter. CONCLUSION: From these data we conclude that the human cornea recovers during organ-culture, especially during the first two weeks. The changes occurring after a fortnight might be related to the artificial culture conditions. Nevertheless, the metabolic status is better than in post-mortem corneas. The changes may be partly avoided by changing the medium after at least two weeks of organ-culture.

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UNLABELLED: Chronic ischemia of the retina and the optic nerve head seems of importance especially in patients with normal-tension glaucoma (NTG). The purpose of this study was to examine the retinal hemodynamics in patients with NTG. PATIENTS: Twenty-five patients with NTG were examined (3 weeks washout period) in this study (age 58 +/- 16 years). The arteriovenous passage (AVP) time and arterial and venous diameters from scanning laser fluorescein angiograms were evaluated by means of digital image analysis. RESULTS: The AVP time in patients with NTG (2.78 +/- 1.1 s) was significantly prolonged (P < 0.0001) compared with healthy subjects (1.58 +/- 0.4 s). No significant correlation was found between arterial and venous diameters, intraocular pressure, blood pressure or calculated perfusion pressure and retinal arteriovenous passage time. CONCLUSION: Patients with NTG showed prolonged retinal passage, which could cause chronic hypoxia. This prolongation of circulation is not correlated with any of the clinical parameters. Thus, a circulatory defect might be a primary factor in the pathogenesis of NTG.

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BACKGROUND: Metabolic changes of the human donor cornea during organ-culture are not at all reflected by the endothelium. Therefore metabolic investigations have become of increasing interest. It was the aim of this study to determine the correlation between glucose and lactate in storage medium and within the cornea itself and to find thereby an additional parameter for glucose metabolism during organ-culture. METHODS: Glucose and lactate were examined in 166 organ-culture medium samples as well as in 106 human corneas by enzymatical optical methods. Investigations were carried out after 1, 7, 15, 21 and 28 days of organ-culture. RESULTS: Glucose consumption was highest during the first two weeks of organ-culture. Glucose concentrations showed a good linear correlation between medium samples and the cornea (r = 0.923). The correlation coefficient for lactate was worse (r = 0.733). CONCLUSION: Glucose and lactate levels in the organ-culture medium can be used as a marker for glucose metabolism in the cornea.

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BACKGROUND: Quantification of glucose and lactate concentrations in human corneal extracts has been performed using spectrophotometry. We employed a bioluminescence technique to obtain a more sensitive assay for glucose and lactate and to reduce the volume of the test sample. MATERIALS AND METHODS: The NAD(P)H bioluminescence assay (Boehringer Mannheim, Germany) was modified for glucose and lactate. Standard curves were established using a standard solution with 0.004 mM and 0.01 mM concentrations of glucose and lactate, respectively. RESULTS: Linear standard curves ranging from 0 to 200 pmol for glucose and from 0 to 250 pmol for lactate were established. The sample volume was reduced from 100 microliters to 25 microliters compared with spectrophotometry. DISCUSSION: The modified bioluminescence technique provides a highly sensitive quantification of glucose and lactate in the human cornea and thus reveals more details of the overall metabolic status of the tissue.

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PURPOSE: Corneas are usually stored for a maximum of approximately 30 days in European cornea banks. Although attempts are being made to prolong culture periods, data on their success are extremely limited to date. The following study was carried out to describe the capacities and limits of the established system. METHODS: Thirty-seven human corneas were stored for < or = 12 weeks under standard eye bank conditions [modified minimal essential medium (MEM), 31 degrees C, closed system]. Twenty-one fresh human corneas served as control. Both the adenylate nucleotides and the glucose and lactate concentrations were measured in the tissue (all cellular layers) by using the bioluminescence technique. The endothelial-cell densities also were determined. RESULTS: Endothelial-cell densities decreased from 2,963.4 +/- 58.7 cells/mm2 (fresh) to 2,649 cell/mm2 after 4 weeks and to 2,087 cells/mm2 after 6 weeks. Storage for periods >6 weeks led to total endothelial necrosis. Biochemical studies showed improving values during the first 4 weeks and acceptable conditions for < or = 6 weeks. CONCLUSION: From these data, we conclude that long-term organ culture in a closed system is limited to approximately 6 weeks and thereby confirm the clinical results of Früh and Böhnke.

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UNLABELLED: Recent studies have shown that the human cornea reflects the metabolic status of the donor. Nevertheless, it has not yet been shown whether this leads to a different tolerance of organ culture and whether these changes are reversible or not. MATERIALS AND METHODS: Eighty-five organ-cultured human corneas were investigated. Endothelial cell density and the concentrations of glucose, lactate, ATP and ADP were determined in each cornea by enzymatic-optical methods. Obduction protocols were examined and five groups of donors could be determined: (1) donors who had died suddenly; (2) donors who had died of malignant processes; (3) donors with septicaemia; (4) renal-insufficient donors; and (5) diabetic donors. RESULTS: Endothelial cell density decreased significantly after 28 days of organ culture. Deswelling for 1 day in a medium containing dextran 500 caused additional cell loss. On the basis of biochemical parameters, the corneas showed recovery after organ culture: especially ATP and ADP concentrations increased. Glucose concentrations decreased and lactate concentration increased in the closed organ culture system. Best recovery was observed in corneas from septic donors and from those who had died of carcinoma. Overall, an equalization of all corneas after the culture period was observed. In contrast, the deswelling period causes deterioration of metabolic status; ATP concentration decreased dramatically, and ADP increase was higher than expected. CONCLUSION: From these data we conclude that there is no donor disease that could lead to exclusion of the cornea from organ culture. In fact, organ culture leads to a recovery of the metabolic status of the human cornea.

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