Need For Corneal Transplantation Research Articles

Systemic IL‐1β production as a consequence of corneal HSV‐1 infection – contribution to the development of Herpes Simplex Keratitis

PurposeHerpes Simplex Virus type‐1 (HSV‐1) infection can result in keratitis, a sight‐threatening disease that is the leading cause of infectious corneal blindness in the western world. HSV‐1 can invade the cornea and remain latent after treatment in the trigeminal ganglia. The pathogenesis of HSK involves a complex interaction between cytokines, chemokines and growth factors, either brought in by inflammatory cells or produced locally. Avoidance of these innate anti‐viral responses can cause lifelong recurrent infection, which in turn can cause progressive corneal scarring, vascularisation, thinning and the need for corneal transplantation to recover vision, often with poor long‐term outcome. This study aimed to investigate peripheral cytokine production in HSK patients with active and inactive infection to identify potential therapeutic targets.MethodsPeripheral blood mononuclear cells and serum were prepared from whole blood taken from both healthy controls and HSK patients during active infection or following treatment. Protein expression levels were analysed by Western Blot. Cytokine levels were determined by multiplex ELISA.ResultsActive corneal HSV‐1 infection resulted in significantly elevated peripheral levels of the pro‐inflammatory cytokine IL‐1b in patients compared to healthy controls. IL‐1β levels remained significantly increased in these patients following treatment. Impaired production of pro‐inflammatory cytokines (including IL‐6, IL‐8 and TNF‐a) and anti‐viral factors (including IL‐12 and IFN‐g) was associated with significantly reduced expression of the transcription factors IRF3 and STAT1 in active patients compared to inactive patients.ConclusionsOur data suggest that dysregulated peripheral production of pro‐inflammatory cytokines and anti‐viral factors may have implications for HSV‐1 viral clearance and recurrent keratitis.

Corneal collagen crosslinking with riboflavin and ultraviolet-A light in progressive keratoconus: Ten-year results

To analyze the 10-year results of corneal collagen crosslinking (CXL) for keratoconus. Department of Ophthalmology, University Hospital, Dresden, Germany. Retrospective interventional case series. The study included eyes treated for progressive keratoconus from 2000 to 2004. Corneal collagen crosslinking was performed by applying riboflavin and ultraviolet-A. The corrected distance visual acuity (CDVA), corneal topography, and endothelial cell count (ECC) were recorded preoperatively and 10 years postoperatively. The study enrolled 24 patients (34 eyes). The mean age of the 18 men and 6 women was 28.4 years ± 7.3 (SD) and the mean follow-up, 131.9 ± 20.1 months. The mean apical keratometry (K) value was 61.5 diopters (D) preoperatively and 55.3 D 10 years postoperatively; the decrease was statistically significant (P<.001). The mean values for maximum K (53.2 D and 49.56 D, respectively) and minimum K (47.5 D and 45.5 D, respectively) were also significantly lower (P<.001). The preoperative and postoperative CDVA were statistically significantly different (P=.002). The mean CDVA improved by 0.14 logMAR over preoperatively; the change was statistically significant (P=.002). The ECC was unchanged. Corneal CXL was effective in treating progressive keratoconus, achieving long-term stabilization of the condition. It was easy to perform, had a good safety profile, and reduced the need for corneal transplantation. No author has a financial or proprietary interest in any material or method mentioned.

Targeted transplantation of human umbilical cord blood endothelial progenitor cells with immunomagnetic nanoparticles to repair corneal endothelium defect.

Corneal endothelial dysfunction involves progressive corneal edema and loss of visual acuity, which result in the need for corneal transplantation. The global shortage of donor corneas limits the development of the surgery. Reconstruction of a bioengineered corneal endothelium might resolve this problem. Various scaffolds have been used, but poor biocompatibility and degradation limit their applications. In this study, a novel method of targeted cellular transplantation without permanent residence of cell carriers in the host was proposed. Human umbilical cord blood endothelial progenitor cells (UCB EPCs) were labeled with CD34 immunomagnetic nanoparticles. The efficiency of the magnet attraction was evaluated in vitro with a simple device simulating the anterior chamber. The UCB EPCs labeled with nanoparticles were transplanted into the anterior chamber of rabbits with magnet attraction. The results indicated that labeling the nanoparticles did not affect the proliferation of the UCB EPCs. The in vitro study indicated that the magnet could directionally attract UCB EPCs labeled with nanoparticles. The in vivo study indicated that the corneas in rabbits transplanted with UCB EPCs labeled with nanoparticles and magnet attraction became relatively transparent with little edema. These results showed that UCB EPCs labeled with CD34 immunomagnetic nanoparticles could be attracted directionally by a magnet and could repair corneal endothelial defects, providing a promising cell therapy for corneal endothelial dysfunction.

Regenerative Cell Therapy for Corneal Endothelium.

Endothelial cell dysfunction as in Fuchs dystrophy or pseudophakic bullous keratopathy, and the limited regenerative capacity of human corneal endothelial cells (HCECs), drive the need for corneal transplant. In response to limited donor corneal availability, significant effort has been directed towards cell therapy as an alternative to surgery. Stimulation of endogenous progenitors, or transplant of stem cell-derived HCECs or in vitro-expanded, donor-derived HCECs could replace traditional surgery with regenerative therapy. Ex vivo expansion of HCECs is technically challenging, and the basis for molecular identification of functional HCECs is not established. Delivery of cells to the inner layer of the human cornea is another challenge: different techniques, from simple injection to artificial corneal scaffolds, are being investigated. Despite remaining questions, corneal endothelial cell therapies, translated to the clinic, represent the future for the treatment of corneal endotheliopathies.

Acute Corneal Hydrops in Keratoconus—New Perspectives

To summarize the current concepts and recent literature regarding the epidemiology, pathogenesis, imaging modalities, and treatment of acute hydrops in keratoconus. Perspective. Review and synthesis of selected literature, with interpretation and perspective. Acute corneal hydrops is an incompletely understood complication of keratoconus, characterized by marked corneal edema caused by a break in Descemet membrane, allowing aqueous to enter the corneal stroma and epithelium. Although usually self-limiting, with clinical signs of edema typically resolving after 3months, it often leaves a vision-impairing scar, necessitating and expediting the need for corneal transplantation. Studies have identified risk factors for developing acute hydrops. Modern imaging modalities such as ultrasound biomicroscopy, anterior segment optical coherence tomography, and invivo confocal microscopy have enlightened us to the microstructural changes that take place during acute hydrops, the factors that influence its duration, and sequelae. Newer treatment regimens have seen a reduction in the duration of corneal edema during acute hydrops, and have improved the survival of corneal grafts after transplantation for resolved hydrops. Effective management of acute corneal hydrops in keratoconus is based on recognizing and addressing the risk factors, treating the acute event effectively and promptly to reduce the duration of edema and its complications, and, ultimately, successful corneal transplantation with acceptable long-term graft survival rates. Improved invivo imaging of the cornea during acute hydrops has led to an enhanced understanding of the pathogenesis and ultrastructural changes of the condition, and in turn has resulted in improved management of the disease.

Scleral lenses for keratoconus and corneal transplant

Successful application of scleral lenses in the management of keratoconus or post corneal transplant can enhance contact lens wear by offering an alternative to corneal lenses when needed, or can avoid or delay the need for corneal transplantation or further surgery.

Clinical presentation and morbidity of contact lens–associated microbial keratitis: a retrospective study

To investigate the clinical presentation, isolated organism, treatment, and morbidity of contact lens-associated microbial keratitis needing hospitalization. This retrospective study included all consecutive patients with contact lens-associated microbial keratitis hospitalized in the Rotterdam Eye Hospital from January 1, 2005, to December 31, 2009. All data regarding epidemiological characteristics, clinical presentation, isolated organism, and treatment were collected from medical records. There were 109 cases (108 patients) of contact lens-associated microbial keratitis hospitalized during the study period. Mean age was 33.3 ± 15.4 (SD) years. Pseudomonas aeruginosa was the most frequently isolated microorganism (68.8%), with minor resistance to gentamicin (2.7%) and ofloxacin (1.3%). At time of presentation, best corrected visual acuity (BCVA) was very poor, with the largest proportion of patients (65.1%) seeing worse than 0.05 Snellen. After intensive treatment, the visual outcome improved considerably, with the largest proportion (67.0%) achieving a BCVA ≥ 0.7 Snellen. Low BCVA at admission was significantly associated with a worse final BCVA. A total of 22 patients (20.2%) required corneal transplantation (three emergency cases). Larger size of stromal infiltrate was significantly associated with the need for corneal transplantation. Microbial keratitis is a serious complication of contact lens wear, with approximately one out of five hospitalized cases requiring corneal transplantation. Ofloxacin, or a combination of gentamicin and cephazolin, still appear to be excellent first-choice therapies in the Netherlands, as little resistance has developed to these antibiotics.

Control of scar tissue formation in the cornea: strategies in clinical and corneal tissue engineering.

Corneal structure is highly organized and unified in architecture with structural and functional integration which mediates transparency and vision. Disease and injury are the second most common cause of blindness affecting over 10 million people worldwide. Ninety percent of blindness is permanent due to scarring and vascularization. Scarring caused via fibrotic cellular responses, heals the tissue, but fails to restore transparency. Controlling keratocyte activation and differentiation are key for the inhibition and prevention of fibrosis. Ophthalmic surgery techniques are continually developing to preserve and restore vision but corneal regression and scarring are often detrimental side effects and long term continuous follow up studies are lacking or discouraging. Appropriate corneal models may lead to a reduced need for corneal transplantation as presently there are insufficient numbers or suitable tissue to meet demand. Synthetic optical materials are under development for keratoprothesis although clinical use is limited due to implantation complications and high rejection rates. Tissue engineered corneas offer an alternative which more closely mimic the morphological, physiological and biomechanical properties of native corneas. However, replication of the native collagen fiber organization and retaining the phenotype of stromal cells which prevent scar-like tissue formation remains a challenge. Careful manipulation of culture environments are under investigation to determine a suitable environment that simulates native ECM organization and stimulates keratocyte migration and generation.

Treatment strategies for corneal ectasia

To review the most recent management strategies for corneal ectasia after keratorefractive surgery. Management options for postoperative ectasia include conservative management with various types of contact lenses such as rigid gas permeable lenses, custom wave front-guided soft contact lenses, hybrid lenses and tandem soft contact lens-rigid gas permeable lenses. Minimally invasive surgical options including corneal ring segment implantation with Intacs, KeraRings or Ferrara rings have shown to have good results in the initial period after insertion. However, there appears to be some evidence that this initial effect may regress with time. Collagen cross-linking is also minimally invasive and has been documented to stop the progression of ectasia and in some cases may cause regression. Recently, techniques combining collagen cross-linking with intracorneal ring segments or with topography-guided excimer laser treatments have shown to have promising results. Early management of ectasia is essential to prevent its progression and to preserve visual potential. There are several management options that are available that may be used to reduce the need for corneal transplantation for these patients.

Corneal collagen crosslinking: new horizons

Corneal collagen crosslinking using the photosensitzer riboflavin and UVA light has been introduced recently as an effective means of stabilizing the cornea in keratoconus and is currently entering mainstream use; the 6-year results have confirmed earlier positive results. Preoperative pachymetry to ensure a stromal thickness of at least 400 µm and individual control of the UVA irradiance of 3 mW/cm2 before each treatment are both mandatory to avoid serious risks. Complications such as keratitis, perforation or scarring are extremely rare. New applications of the technique are currently being explored, such as the treatment of post-laser in situ keratomileusis ectasia, pellucid marginal degeneration, therapy-refractive keratitis or bullous keratopathy. Thanks to crosslinking, the need for corneal transplantation should be reduced significantly in the future in various corneal disorders.

Topography-guided Transepithelial Surface Ablation Followed by Corneal Collagen Cross-linking Performed in a Single Combined Procedure for the Treatment of Keratoconus and Pellucid Marginal Degeneration

To evaluate a combination of topography-guided custom ablation and corneal collagen cross-linking (CXL) in a single procedure for the treatment of keratectasia. Twelve eyes of 12 patients with keratectasia were treated with topography-guided custom ablation and CXL. Topography-guided custom ablation was performed using a transepithelial technique with the iVIS Suite 1 kHz flying spot excimer laser. Collagen cross-linking was performed immediately after topography-guided custom ablation, according to standard protocol. Postoperative follow-up examinations were performed at 1, 3, 6, and 12 months. Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), refractive change, corneal topography, and pachymetry were analyzed pre- and postoperatively. Mean UCVA increased from 20/1000 preoperatively to 20/125 12 months postoperatively. Mean BSCVA increased from 20/57 to 20/35, with no loss of lines of visual acuity. Mean astigmatism was reduced from 5.40+/-2.13 diopters (D) to 2.70+/-1.44 D, and keratometric asymmetry decreased from 6.38+/-1.02 D to 2.76+/-0.73 D. Only minor changes in posterior corneal surface elevation and stability of refraction were found, confirming that no progression of ectasia occurred during the observation time. A combination of topography-guided custom ablation and CXL improved patients' visual, refractive, and topography outcomes and halted the progression of keratectasia within the observation period of 12 months. This method may postpone or eliminate the need for corneal transplantation in suitable cases with keratectasia.

Adaptação de lente de contato gelatinosa especial para ceratocone

To evaluate the fitting and use of a soft contact lens in keratoconic patients. Retrospective study on 80 eyes of 66 patients, fitted with a special soft contact lens for keratoconus, at the Contact Lens Section of UNIFESP and private clinics. Keratoconus was classified according to degrees of disease severity by keratometric pattern. Age, gender, diagnosis, keratometry, visual acuity, spherical equivalent (SE), base curve and clinical indication were recorded. Of 66 patients (80 eyes) with keratoconus the mean age was 29 years, 51.5% were men and 48.5% women. According to the groups: 15.0% were incipient, 53.7% moderate, 26.3% advanced and 5.0% were severe. The majority of the eyes of patients using contact lenses (91.25%) achieved visual acuity better than 20/40. To 88 eyes 58% were tihed with lens with spherical power (mean -5.45 diopters) and 41% with spherocylinder power (from -0.5 to -5.00 cylindrical diopters). The most frequent base curve was 7.6 in 61% of the eyes. The main reasons for this special lens fitting were due to reduced tolerance and poor fitting pattern achieved with other lenses. The special soft contact lens is useful in fitting difficult keratoconic patients by offering comfort and improving visual rehabilitation that may allow more patients to postpone the need for corneal transplant.

Le kératocône : options chirurgicales actuelles

The treatment of keratoconus is in part dependant on the severity of the disease process. When contact lenses fail because of patient intolerance or insufficient acuity to meet the patient's needs, penetrating keratoplasty is the usual surgical modality considered for satisfactory visual rehabilitation. Keratoconus is considered to be a contraindication for incisional refractive surgery such as radial keratotomies or LASIK because of the corneal instability conferred by these procedures. When the cornea is transparent, INTACS implantation is a refractive modality that may improve visual function and in some instances prevent the need for corneal transplantation in select patients with keratoconus.

Current surgical options for keratoconus

The treatment of keratoconus is partly dependent on the severity of the disease process. When contact lenses fail because the patient is intolerant or they do not provide sufficient acuity to meet the patient’s needs, penetrating keratoplasty is the usual surgical modality for adequate visual rehabilitation. Keratoconus is considered a contraindication to incisional refractive surgery such as radial keratotomy and laser in situ keratomileusis because of the corneal instability conferred by these procedures. When the cornea is transparent, intrastromal corneal ring implantation is a refractive modality that may improve visual function and, in select keratoconus patients, obviate the need for corneal transplantation.

Ceratocone: correlação entre grau evolutivo e padrão topográfico com o tipo de lente de contato adaptada

PURPOSE: To determine associations between degrees of severity and topographical patterns of keratoconus with fitted contact lenses (CL). METHODS: Retrospective study of 454 patients (881 eyes) with keratoconus, 746 fitted with contact lenses, from July 1996 to June 2000. Keratoconus was classified according to degrees of severity and topographical pattern. The first tested contact lens was the spherical rigid gas permeable. When it did not achieve the desired fitting, the bicurve rigid gas permeable and other designs were tried, in search of an apical clearance or slight apical touch fitting relationship. RESULTS: For 15 (3.3%) patients glasses were prescribed; 111 eyes (12.6%) remained uncorrected; 746 (84.68%) eyes were fitted with contact lenses; for 39 eyes (4.44%) of 39 patients (8.6%) penetrating keratoplasty was recommended. The most common degree of severity found was advanced (575 eyes - 66.86%), followed by the mild variety (160 eyes -18.6%). The average keratometric value of the flattest meridian (K) was 47.80 (±3.73) for the eyes fitted with soft CL; 49.03 (±3.7) for the spherical rigid gas permeable contact lenses; of 51.62 (±3.6) for the bicurve contact lenses and 51.14 (±3.5) for the piggyback system. Concerning the topographical pattern, the most frequent was inferior peripheral cone (436 eyes - 50.7%), followed by central asymmetrical cone (348 eyes - 40.46%). In the right eye, the analysis of the variables, topographical pattern and kind of fitted lens showed a statistically significant association (p=0.045) of toric soft contact lenses and piggyback system with a higher percentage of fittings in central cone. Concerning the rigid spherical and bicurve lenses, the fitting percentage was similar in relation to the found topographical pattern. In the left eye, statistically significant associations were not observed, only tendencies. CONCLUSION: Spherical contact lenses can be fitted to the majority of patients with keratoconus, but it is important to rely on other designs to fit the advanced and severe cases. This allows most patients to postpone the need for corneal transplant. Toric soft contact lenses and piggyback system were more frequently fitted to central cones; whereas in inferior peripheral cones, spherical and bicurve contact lenses were those more used.

Ocular Injuries Caused by Mustard Gas: Diagnosis, Treatment, and Medical Defense

Sulfur mustard has been used as a vesicant chemical warfare agent. To investigate the ocular damage it causes, we studied the effects on chemical casualties in the Iran-Iraq War. The patient population consisted of more than 5,000 chemical casualties, both military and civilian. The range of ocular damage was wide. The most common ocular effects were conjunctivitis and photophobia. Patients with significant corneal involvement are at risk for corneal ulceration and rarely for anterior chamber scarring and neovascularization, any of which would result in prolonged disability. In conclusion, the eye is the organ most sensitive to sulfur mustard vapor. Ocular injuries generally heal completely. In severe cases, blindness may occur. The need for corneal transplantation is rare.

Visual and tear function improvement after superficial phototherapeutic keratectomy (PTK) for mid-stromal corneal scarring.

To study the changes in visual and tear film function following superficial excimer laser phototherapeutic keratectomy in patients with mid-stromal corneal scars. Fourteen eyes of 14 patients with mid-stromal corneal scars seen at the Department of Ophthalmology at Kobe Kaisei Hospital underwent superficial phototherapeutic keratectomy (PTK). The subjects underwent routine ophthalmic examinations, corneal sensitivity measurements, tear film break-up time (BUT), Schrimer test and tear film lipid layer interferometry. Thirty eyes of 15 normal control subjects were also studied. The patients and the control subjects were compared for pre-PTK tear function parameters and tear film lipid layer interferometry grade. The alterations in these parameters within 6 months following PTK were also determined. Visual improvement was achieved in 12 eyes (86%). A hyperopic shift was observed in all eyes. The average pre-PTK corneal sensitivity and tear film BUT were lower in patients compared with control subjects before PTK. Tear film lipid layer interferometry grades were also higher in the patients than the controls before PTK. All these parameters improved gradually and significantly after PTK. Schirmer test results did not show any significant alterations after PTK. We conclude that PTK is an effective means of treating corneal scars and attaining visual improvement, even in cases with deeper corneal involvement, and may obviate the need for corneal transplantation. Simultaneous improvements in corneal sensitivity and tear film stability suggest favourable effects of PTK on the ocular surface.

Screening of human corneas for herpes simplex virus by tissue culture and polymerase chain reaction.

Superficial eye infections by herpes simplex virus (HSV) constitute a major cause of corneal disease, necessitating the need for corneal transplantation in many patients. Eighty-three corneas from 46 post-mortem donors received from the David Lucas Eye Bank in Manchester were analyzed by Vero cell culture and the polymerase chain reaction (PCR) technique to detect HSV. There was no evidence of a characteristic cytopathic effect in any of the cultures. A 350-bp PCR product corresponding to the HSV thymidine kinase (TK) was detected by southern blotting in only 2.4% (2/83) of samples. In contrast, approximately 70% of samples yielded a 758-bp PCR product. Although this low prevalence of HSV in corneas may be encouraging, it is high for the actual transplantation program if the viral DNAs maintain their abilities to replicate.

Treatment of Reis-Bücklers' Corneal Dystrophy by Removal of Subepithelial Fibrous Tissue

We treated five eyes of three patients with Reis-Bücklers' corneal dystrophy by blunt dissection of the subepithelial fibrous tissue layer. The postoperative follow-up ranged from four months to three years. Four of the five eyes had improved vision, and all four symptomatic eyes had cessation of the recurrent erosions. This simple effective technique eliminated the need for corneal transplantation.