Recommendations for rosacea diagnosis, classification and management: update from the global ROSacea COnsensus 2019 panel.

BACKGROUND: A transition from a subtyping to a phenotyping approach in rosacea is underway, allowing individual patient management according to presenting features instead of categorization by predefined subtypes. The ROSacea COnsensus (ROSCO) 2017 recommendations further support this transition and align with guidance from other working groups. OBJECTIVES: To update and extend previous global ROSCO recommendations in line with the latest research and continue supporting uptake of the phenotype approach in rosacea through clinical tool development. METHODS: Nineteen dermatologists and two ophthalmologists used a modified Delphi approach to reach consensus on statements pertaining to critical aspects of rosacea diagnosis, classification and management. Voting was electronic and blinded. RESULTS: Delphi statements on which the panel achieved consensus of ≥ 75% voting 'Agree' or 'Strongly agree' are presented. The panel recommends discussing disease burden with patients during consultations, using four questions to assist conversations. The primary treatment objective should be achievement of complete clearance, owing to previously established clinical benefits for patients. Cutaneous and ocular features are defined. Treatments have been reassessed in line with recent evidence and the prior treatment algorithm updated. Combination therapy is recommended to benefit patients with multiple features. Ongoing monitoring and dialogue should take place between physician and patients, covering defined factors to maximize outcomes. A prototype clinical tool (Rosacea Tracker) and patient case studies have been developed from consensus statements. CONCLUSIONS: The current survey updates previous recommendations as a basis for local guideline development and provides clinical tools to facilitate a phenotype approach in practice and improve rosacea patient management. What's already known about this topic? A transition to a phenotype approach in rosacea is underway and is being recommended by multiple working groups. New research has become available since the previous ROSCO consensus, necessitating an update and extension of recommendations. What does this study add? We offer updated global recommendations for clinical practice that account for recent research, to continue supporting the transition to a phenotype approach in rosacea. We present prototype clinical tools to facilitate use of the phenotype approach in practice and improve management of patients with rosacea.

[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 .

The in vitro activity of selected defensins against an isolate of Pseudomonas in the presence of human tears.

BACKGROUND/AIMS: Pseudomonas aeruginosa is a major cause of severe bacterial keratitis and remains a difficult clinical entity to treat successfully with the current arsenal of antimicrobial agents. Defensins are small cationic peptides with broad in vitro antimicrobial activity and are potential ocular therapeutic agents. The authors characterised the in vitro activity of defensins NP-1 and NP-3a against P aeruginosa in the presence of human tears. METHODS: A clinical Pseudomonas isolate was grown to mid-log phase, and 1 x 10(6 )colony forming units were exposed to the peptides (200 microg/ml) for up to 2 hours in the presence of varying concentrations (10-70%) of human tears. RESULTS: For both peptides in the presence of 10% tears, >3 log units of killing was achieved within 30 minutes. In 70% tears, NP-1 produced >1 log unit of killing at 2 hours, indicating that, although reduced, its activity remained significant. In 20% tears, NP-3a demonstrated 2 log units of killing at 2 hours; however, the antimicrobial activity of this defensin was completely inhibited in the presence of 70% tears. CONCLUSION: These in vitro data suggest that while the microbicidal activity of some defensins may be diminished at the ocular surface in vivo, significant activity is still possible with certain peptides.

No effect of concanavalin A on the corneal graft reaction.

Penetrating corneal homografts were performed in albino rabbits. The experimental group received grafts soaked in a solution of concanavalin A; the control group received grafts soaked in lactated Ringer's solution. Animals with technically successful grafts were subsequently exposed to an additional antigenic stimulus from the corneal donor via skin grafting. This procedure produces a uniformly high rate of corneal graft rejection. The two groups were compared for the frequency and onset of the graft reaction. Results demonstrated no difference between control and experimental groups. The significance of these findings is discussed.

Myopia and refractive error in dogs.

The refractive error of 240 phakic dogs of various breeds was measured using streak retinoscopy and averaged (-0.27 +/- 1.41 D relative to infinity). Analysis by breed showed that the German Shepherd, Rottweiler, and Miniature Schnauzer breeds had an increased prevalence of myopia with an average refractive error of -0.86 +/- 1.31 D, -1.77 +/- 1.84 D, and -0.66 +/- 1.05 D, respectively. Myopia also was found in older dogs with marked nuclear sclerosis of the crystalline lens. Fifty-three percent of all German Shepherd dogs in a veterinary clinic population (n = 58 eyes) had a myopic refraction of greater than or equal to -0.50 D; 64% of all Rottweiler dogs (n = 28 eyes) were myopic. An in-depth investigation of German Shepherd dogs, using A-scan ultrasonography, photokeratoscopy, and streak retinoscopy, was done at Guide Dogs for the Blind (San Rafael, CA). By contrast with the results obtained in the veterinary clinic population, the overall average refractive error of guide dog German Shepherd dogs (n = 106 eyes) was +0.19 +/- 0.81 D, and only 15% of these dogs were myopic. The axial length and corneal curvature of myopic eyes did not differ significantly from nonmyopic eyes.

Making sense of refractive surgery in 2001: why, when, for whom, and by whom?

Surgical alteration of the focusing or refractive properties of the eye has been performed on millions of patients. An array of procedures to correct myopia, hyperopia, astigmatism, and presbyopia have been introduced over the past 25 years with varying degrees of success. Improved technology has increased patient and physician satisfaction and enthusiasm. Currently available surgical procedures can be categorized as incisional, surface-altering, lamellar, and intraocular. The choice of procedure depends on individual patient indications and contraindications based on results of ocular examinations, eg, corneal pachymetry to measure corneal thickness, keratometry to measure the corneal curvature, basal tear secretory rate, and dark-adapted pupil size. The postoperative uncorrected visual acuity depends, in large part, on the quality of the preoperative evaluation and refraction. Before scheduling a patient for surgery, the ophthalmologist must ensure that the patient understands the potential risks of the procedure and has realistic expectations for the postoperative level and quality of uncorrected visual acuity. Postoperative complications include corneal flap displacement, undercorrection and overcorrection, and epithelial ingrowth under the corneal flap and inflammatory keratitis. Postoperative dry eye, infection, and inflammation are usually treated medically. Ongoing technological innovations to customize the surgical approach to an individual patient's eye continue to improve outcomes.

Iron deposition in the corneal graft. Another corneal iron line.

Linear iron deposits in the corneal epithelium are well-documented phenomena in a variety of circumstances, both normal and pathologic. A characteristic annular pigmented line, appearing clinically as an "iron" line, occurred in the donor epithelium of approximately 13% of corneal grafts with retained sutures. Eight cases of normally functioning grafts had iron lines located just central to the sutures. These lines appeared at various intervals postoperatively and did not correlate with age or race. They were frequently found in association with other surface-related epithelial and subepithelial phenomena and were believed to be related to peripheral corneal topography and the lid-cornea interface. Although they are clinically iron, their precise histochemistry, cause, source, and natural history are yet to be determined.

Extended-wear aphakic soft contact lenses after penetrating keratoplasty.

Seven patients undergoing aphakic keratoplasty or combined keratoplasty and cataract extraction were fitted with a single type of high-water-content, extended-wear, aphakic soft contact lens (Permalens). Six patients were fitted early after keratoplasty, ie, before the removal of the sutures and while they were still receiving corticosteroid drops (1% prednisolone acetate). The patients were followed up at close intervals with high-magnification serial corneal photography. Complications of extended wear included superficial neovascularization, punctate epithelial keratitis, and variable visual acuity. Our results suggest that although extended-wear aphakic soft contact lenses may be an acceptance form of visual rehabilitation in selected patients who undergo transplantation, they are frequently problematic. In addition, fitting of these lenses should be withheld until after the removal of the sutures, and patients should be followed up at closer intervals than the patients with extended-wear aphakic soft contact lenses who have not undergone keratoplasty.

Dendritic corneal lesions associated with soft contact lens wear.

Two cases of dendritic lesions associated with soft contact lens wear occurred that were referred as cases of herpes simplex keratitis. Lesions resolved after temporary discontinuation of soft lens wear and conversion to thermal sterilization. The pseudodendrite is presumed to result from a toxic or hypersensitivity reaction to contact lens material or to components of chemical sterilization systems. Several dendritic lesions may be confused with herpes simplex. The soft contact lens associated pseudodendrite is added to this list. Accurate diagnosis can be made by careful attention to the clinical history and the morphologic features of the dendrite in most cases.

The effect of penetrating keratoplasty on contrast sensitivity in keratoconus.

Complaints of visual distortion often precede a decrement in visual acuity in keratoconus. We studied seven patients with keratoconus who had undergone keratoplasty in one eye and whose Snellen visual acuity measurements were equal in the grafted and nongrafted eyes. Subjects were examined clinically; we then measured contrast thresholds for seven spatial frequencies of computer-generated sinusoidal gratings after optimal contact lens correction. Results indicate that nongrafted keratoconic eyes demonstrate abnormal contrast sensitivity, even with good visual acuity measurements. Eyes with clear corneal grafts and with visual acuities comparable to nongrafted eyes fell within the 95% confidence limits of the normal contrast sensitivity curve. The findings confirm that corneal distortion or opacity in the optimally corrected keratoconic eye may account for notable visual dysfunction and that keratoplasty improves not only Snellen visual acuity but contrast sensitivity as well.

Uses of thrombin in ocular surgery. Effect on the corneal endothelium.

Thrombin is a hemostatic factor that induces platelet aggregation and catalyzes the conversion of fibrinogen to fibrin. The potential for its increasing application to a variety of anterior and posterior segment surgery led us to investigate the in vitro effect of thrombin on the corneal endothelium in a sheep model. We examined freshly excised sheep corneas stained with alizarin red and trypan blue after exposure to two different concentrations of thrombin for four hours. The structure of the corneal endothelium appeared to be intact even after prolonged exposure to thrombin at concentrations of 100 and 1000 U/mL. Thrombin appears to be nontoxic to the corneal endothelium in this experimental model.

The effect of fluorouracil on the corneal endothelium.

The utility of the antiproliferative agent fluorouracil has been demonstrated recently in glaucoma-filtering surgery and in the management of proliferative vitreoretinopathy after vitrectomy. Because of the potential for contact with the corneal endothelium, its toxicity to the endothelium is an important consideration. The effect of fluorouracil on corneal endothelial integrity in an in vitro animal model was studied. Freshly excised sheep corneal buttons were exposed to increasing concentrations of fluorouracil for four hours and were subsequently evaluated microscopically using vital staining with alizarin red and trypan blue. Exposure to normal saline and chlorhexidine gluconate was used to establish negative- and positive-staining controls. Corneal buttons exposed to normal saline or to 1.0 mg/mL or less of fluorouracil had intact endothelial monolayers that completely excluded trypan blue. Corneal buttons exposed to chlorhexidine gluconate or to 10 mg/mL of fluorouracil, however, had severely or totally disrupted endothelial monolayers in which the remaining cells, if any, all had blue-staining nuclei. These results suggest that the threshold concentration for fluorouracil toxicity to corneal endothelium lies between 1 and 10 mg/mL when exposure time is four hours.

Posterior corneal vesicles.

Two male and four female patients had posterior corneal vesicles and scalloped lesions. Ages ranged from 7 to 24 years. Uncorrected visual acuities were 6/6 or better OU. All cases were unilateral. There was no other ocular abnormality. The lesions were at the level of Descemet's membrane and endothelium. Results of specular microscopic examination suggested that the scalloped lesions could be the result of coalescence of vesicular defects. Several vesicles were surrounded by grayfish halos. The remainder of the cornea was normal. Thirty family members were found to be unaffected. These lesions must be differentiated from those in posterior polymorphous dystrophy congenital glaucoma, and forceps injury. Previous reports have implied a herpetic origin; although their etiologic character is not known, the present study does not support this conclusion.

Contrast sensitivity after penetrating keratoplasty.

Contrast sensitivity testing in the corneal transplant patient may enhance our assessment of visual performance, which is traditionally evaluated using Snellen acuity only. To evaluate contrast sensitivity function after penetrating keratoplasty, we studied 29 patients with anatomically successful corneal grafts and a best corrected visual acuity of 20/50 or better. Graft patients were compared with an age-matched control group including persons with comparable visual acuities without ocular disease. In addition to a complete ophthalmic examination, all subjects underwent contrast sensitivity testing using a computer-generated sinusoidal grating system as well as a commercially available contrast sensitivity wall chart. Data indicate that, despite comparable Snellen visual acuity, the contrast sensitivity curves for graft patients were depressed overall compared with those of normal subjects except at the lowest spatial frequency. However, comparison of grafted eyes to contralateral eyes with corneal disease in a small subset of patients with bilateral disease shows a trend toward higher contrast sensitivity values in the eyes that had been operated on. These data suggest that despite an improvement in contrast sensitivity with penetrating keratoplasty, an eye with a corneal transplant is not entirely normal from a visual standpoint. Nonacuity parameters may be important indexes for assessing real-world visual function in the graft patient, although the clinical role of these tests is not yet completely defined.

Personality trends in keratoconus. An analysis.

Patients with keratoconus frequently are described as having peculiar personality characteristics, despite the lack of controlled studies in the ophthalmologic or psychiatric literature. We studied 109 subjects, using a standardized personality inventory (the Millon Clinical Multiaxial Inventory) that measures 20 personality scales-both normal and pathologic. Subjects were divided into three age-matched groups: (1) patients with keratoconus, (2) patients with other chronic eye diseases, and (3) normal controls. Results indicated that although chronic eye disease, including keratoconus, did have an impact on personality functioning in young and middle-aged adults, no specific complex of personality characteristics attributable to keratoconus could be identified. Patients with keratoconus differed from normal controls in much the same way as did patients with other chronic eye diseases, being less conforming and more passive-aggressive, paranoid, and hypomanic. They tended to more disorganized patterns of thinking and scored higher on substance abuse indicators. The influence of keratoconus on personality may be a function of the timing and nature of its onset in the context of the patient's psychosocial development.

Polymorphic amyloid degeneration of the cornea. A clinical and histopathologic study.

The occurrence of polymorphic punctate and filamentous opacities in the axial cornea of patients in the fourth decade of life and older represents a distinct clinical entity. The glass-like deposits are usually in the deeper layers of the cornea and are associated with normal intervening stroma. Although it is not a cause of visual dysfunction, this disorder may be confused with lattice corneal dystrophy or with the corneal deposits in some dysproteinemias. Common clinical findings were found in 14 patients, and these findings were contrasted with the findings in lattice corneal dystrophy. Family studies failed to demonstrate heritability, and lesions were found in older patients only. Histopathologic examination identified the lesions as amyloid. The findings suggest that his disorder should be classified as a corneal degeneration. "Polymorphic amyloid degeneration" is a descriptive for this condition.

Keratopathy associated with intracorneal glass.

A progressive nonedematous keratopathy developed in a 36-year-old patient after she was struck in the eye by glass fragments. Biopsy material that was examined by electron microscopy and electron beam microanalysis demonstrated the presence of intracorneal glass fragments, which could not be detected clinically. Retained intracorneal glass, generally thought to be completely inert, can be associated with a chronic keratopathy.

Conjunctival transplantation. Autologous and homologous grafts.

Autologous conjunctival transplants have been used successfully for restoration of damaged ocular surfaces. Homologous (allogeneic) conjunctival grafts have been explored less systematically. We developed a nonhuman primate model for comparison of autologous and homologous conjunctival transplantation in order to assess the clinical viability and immunopathologic characteristics of these grafts. Autologous or homologous grafts were performed in nine adult rhesus monkeys. Both autologous and homologous grafts were compared for clinical viability and immunopathologic change. Clinical results suggest that, although homologous grafts incited a greater inflammatory and scarring response, there was minimal graft shrinkage and a normal surface epithelium. Immunopathologic studies using laminin, bullous pemphigoid antigen, and fibronectin indicate that, despite the increased inflammatory response seen in homografts, the epithelial surface is normal. With our increasing ability to modulate the immune response, conjunctival homografts may play a role in restoration of the ocular surface.

Acanthamoeba sclerokeratitis. Determining diagnostic criteria.

Acanthamoeba infection of the cornea is an entity now recognized with increasing frequency. We saw two cases of Acanthamoeba sclerokeratitis in contact lens wearers in whom scleritis (anterior and posterior) played a central role in the clinical course of the disease. Scleritis is probably a more common component of Acanthamoeba infection than has generally been acknowledged. Posterior scleritis has not, to our knowledge, been reported previously in this disorder. The clinical diagnosis of Acanthamoeba infection has often been missed due to lack of a definition of the historical and clinical criteria by which this disease is characterized. We reviewed the 26 previously reported cases and suggest a set of criteria that can be used to establish an early diagnosis. Historical criteria include minor corneal trauma, exposure to soil or standing water, or contact lens wear. Clinical characteristics include severe pain, infiltrative (often ring-shaped) stromal keratitis, variable anterior uveitis, epithelial erosion, scleritis, standard bacterial culture negativity, chronicity, and lack of response to antimicrobial agents.

Corneal posterior crocodile shagreen and polymorphic amyloid degeneration.

Globes were obtained post mortem from a 75-year-old patient who had both corneal posterior crocodile shagreen and polymorphic amyloid degeneration. The crocodile shagreen was typified by grayish, polygonal opacities with indistinct edges and separated by clear lines. The cloudy area involved the central two thirds of the corneas and included the posterior two thirds of the stroma, with increasing posterior density. The polymorphic amyloid degeneration was typical, demonstrating polymorphic punctate and filamentous deposits in the deeper corneal layers. The deposits appeared white in direct illumination and refractile in indirect illumination. Transmission electron microscopy revealed sawtoothlike configurations of the stromal collagen lamellae that corresponded to the central cloudy opacities seen clinically. The minute deposits were found to be amyloid by histochemical staining and electron microscopy.