Berthold Seitz

Dysfunctional Tear Syndrome A Delphi Approach to Treatment Recommendations

Purpose: To develop current treatment recommendations for dry eye disease from consensus of expert advice. Methods: Of 25 preselected international specialists on dry eye, 17 agreed to participate in a modified, 2-round Delphi panel approach. Based on available literature and standards of care, a survey was presented to each panelist. A two-thirds majority was used for consensus building from responses obtained. Treatment algorithms were created. Treatment recommendations for different types and severity levels of dry eye disease were the main outcome. Results: A new term for dry eye disease was proposed: dysfunctional tear syndrome (DTS). Treatment recommendations were based primarily on patient symptoms and signs. Available diagnostic tests were considered of secondary importance in guiding therapy. Development of algorithms was based on the presence or absence of lid margin disease and disturbances of tear distribution and clearance. Disease severity was considered the most important factor for treatment decision-making and was categorized into 4 levels. Severity was assessed on the basis of tear substitute requirements, symptoms of ocular discomfort, and visual disturbance. Clinical signs present in lids, tear film, conjunctiva, and cornea were also used for categorization of severity. Consensus was reached on treatment algorithms for DTS with and without concurrent lid disease. Conclusion: Panelist opinion relied on symptoms and signs (not tests) for selection of treatment strategies. Therapy is chosen to match disease severity and presence versus absence of lid margin disease or tear distribution and clearance disturbances.

Measurement of accommodation after implantation of an accommodating posterior chamber intraocular lens.

Purpose: To analyze techniques of measuring accommodation after implantation of an accommodating posterior chamber intraocular lens (PC IOL). Setting: Department of Ophthalmology and University Eye Hospital, University Erlangen‐Nürnberg, Erlangen, Germany. Methods: This prospective study analyzed 23 eyes of 23 patients (aged 41 to 87 years) after cataract surgery and PC IOL implantation (1 CU®, HumanOptics) 4 weeks and 3 and 6 months after surgery. The results were compared to those in an age‐matched control group (n = 20) 6 months after surgery. The following methods were used to measure accommodation: dynamic with objective techniques (PlusOptix PowerRefractor® videorefractometry, streak retinoscopy) and subjective techniques (subjective near point [push‐up test, accommodometer], defocusing); static with pharmacologic stimulation after pilocarpine 2% eyedrops directly (conventional refractometry); indirectly (change in the anterior chamber depth [ACD] with Zeiss IOLMaster®). Results: Results at 6 months, given as mean ± SD (range), in the study and control groups, respectively, were as follows: near visual acuity (Birkhäuser reading charts at 35 cm) with distance correction, 0.32 ± 0.11 (0.20 to 0.60) and 0.14 ± 0.10 (0.05 to 0.30); accommodation amplitude (diopters) by PowerRefractor, 1.00 ± 0.44 (0.75 to 2.13) and 0.35 ± 0.26 (0.10 to 0.65), by retinoscopy, 0.99 ± 0.48 (0.13 to 2.00) and 0.24 ± 0.21 (–0.13 to +0.75), by subjective near point, 1.60 ± 0.55 (0.50 to 2.56) and 0.42 ± 0.25 (0.00 to 0.75), and by defocusing, 1.46 ± 0.53 (1.00 to −2.50) and 0.55 ± 0.33 (0.25 to 0.87). The mean ACD decrease (mm) was 0.78 ± 0.12 (0.49 to 1.91) and 0.16 ± 0.09 (0.00 to 0.34) after pilocarpine 2% eyedrops, indicating a mean accommodation of 1.40 D and 0.29 D, respectively, based on Gullstrands model eye (P = .001). The lowest fluctuation between follow‐ups was with the subjective near point and the defocusing techniques followed by ACD decrease with the IOLMaster. Conclusions: Accommodation after implantation of an accommodating PC IOL should be assessed with several techniques, including subjective and objective, to differentiate true pseudophakic accommodation from pseudoaccommodation. Researchers should be aware of the different variability and consistency of measurements with each technique over time.

Ic3d Classification of Corneal Dystrophies—edition 2

Purpose: To update the 2008 International Classification of Corneal Dystrophies (IC3D) incorporating new clinical, histopathologic, and genetic information. Methods: The IC3D reviewed worldwide peer-reviewed articles for new information on corneal dystrophies published between 2008 and 2014. Using this information, corneal dystrophy templates and anatomic classification were updated. New clinical, histopathologic, and confocal photographs were added. Results: On the basis of revisiting the cellular origin of corneal dystrophy, a modified anatomic classification is proposed consisting of (1) epithelial and subepithelial dystrophies, (2) epithelial–stromal TGFBI dystrophies, (3) stromal dystrophies, and (4) endothelial dystrophies. Most of the dystrophy templates are updated. The entity “Epithelial recurrent erosion dystrophies” actually includes a number of potentially distinct epithelial dystrophies (Franceschetti corneal dystrophy, Dystrophia Smolandiensis, and Dystrophia Helsinglandica) but must be differentiated from dystrophies such as TGFBI-induced dystrophies, which are also often associated with recurrent epithelial erosions. The chromosome locus of Thiel-Behnke corneal dystrophy is only located on 5q31. The entity previously designated as a variant of Thiel-Behnke corneal dystrophy on chromosome 10q24 may represent a novel corneal dystrophy. Congenital hereditary endothelial dystrophy (CHED, formerly CHED2) is most likely only an autosomal recessive disorder. The so-called autosomal dominant inherited CHED (formerly CHED1) is insufficiently distinct to continue to be considered a unique corneal dystrophy. On review of almost all of the published cases, the description appeared most similar to a type of posterior polymorphous corneal dystrophy linked to the same chromosome 20 locus (PPCD1). Confocal microscopy also has emerged as a helpful tool to reveal in vivo features of several corneal dystrophies that previously required histopathologic examination to definitively diagnose. Conclusions: This revision of the IC3D classification includes an updated anatomic classification of corneal dystrophies more accurately classifying TGFBI dystrophies that affect multiple layers rather than are confined to one corneal layer. Typical histopathologic and confocal images have been added to the corneal dystrophy templates.

Implantation of a new accommodative posterior chamber intraocular lens.

PURPOSE A new, potentially accommodative posterior chamber lens (PCIOL) was designed based on principles elaborated by Hanna using finite element computer simulation methods. We report 3-month postoperative results in patients. METHODS In a prospective study, 12 eyes of 12 patients (age 45 to 87 yr) underwent phacoemulsification for cataracts and PCIOL implantation. The PCIOL, 1 CU, has haptics designed for anterior optic movement following ciliary muscle contraction. Patients were examined postoperatively after 1 and 2 days, 1, 2 and 6 weeks, and 3 months, and results were compared with a control group of 12 eyes that received standard PMMA or acrylic PCIOLs. RESULTS Surgery was uncomplicated and all PCIOLs were well-tolerated and stable with good centration in the capsular bag. The results were (mean +/- SD [range] and median; 1 CU versus control PCIOL): near visual acuity (Birkhäuser reading chart at 35 cm) with best distance correction 0.34 +/- 0.17 (0.2 to 0.6), 0.3 (J10-J1, median J7) versus 0.15 +/- 0.07 (0.1 to 0.3), 0.15 (J16-J7, median J13), P=.001; subjective near point 59 +/- 10 cm (40 to 100 cm), 53.5 cm versus 93 +/- 20 cm (64 to 128 cm), 86 cm, P=.004; retinoscopic accommodative range 1.2 +/- 0.4 D (0.63 to 1.5 D), 1.2 D versus 0.2 +/- 0.19 D (-0.25 to 0.5 D), 0.25 D, P < .001; decrease of anterior chamber depth after 2% pilocarpine 0.63 +/- 0.16 mm (0.40 to 0.91 mm), 0.63 mm versus 0.15 +/- 0.05 mm (0.08 to 0.20 mm), 0.17 mm, P < .001. CONCLUSIONS The new PCIOL appears to be safe at short to medium term. Our results indicate pseudophakic accommodation secondary to focus shift with this PCIOL. Additional larger and long-term studies are necessary for exact evaluation of safety and accommodative power of this new PCIOL.

A randomized, double-blind, phase 2 study of erythropoietin in optic neuritis

Based on findings in animal models of autoimmune optic nerve inflammation, we have assessed the safety and efficacy of erythropoietin in patients presenting with a first episode of optic neuritis.

GS-101 Antisense Oligonucleotide Eye Drops Inhibit Corneal Neovascularization Interim Results of a Randomized Phase II Trial

PURPOSE Pathologic corneal neovascularization not only reduces corneal transparency and visual acuity, but also is one of the most significant preoperative and postoperative risk factors for graft rejection after corneal transplantation. The aim of this study was to test tolerability and efficacy of gene signal (GS)-101 eye drops, an antisense oligonucleotide against insulin receptor substrate-1, versus placebo on inhibition of progressive corneal neovascularization. DESIGN Randomized, double-blind, multicenter, phase II clinical study. PARTICIPANTS AND CONTROLS Interim analysis on 40 patients with progressive corneal neovascularization resulting from various underlying diseases being nonresponsive to conventional therapy. INTERVENTIONS Four groups of 10 patients were treated for 3 months in this dose-finding study comparing 3 doses of GS-101 (eye drops twice daily; 43, 86, and 172 microg/day total) with placebo (10 patients per group). MAIN OUTCOME MEASURES The primary end point was the area covered by pathologic corneal blood vessels, which was measured morphometrically on digitized slit-lamp pictures using image analysis techniques. RESULTS GS-101 eye drops were well tolerated. All serious and 95% of all other adverse events were categorized by the investigators as unrelated. In 3 patients, there was a potentially related side effect of ocular surface discomfort. At a dose of 86 microg/day (43 microg/drop), GS-101 eye drops produced a significant inhibition and regression of corneal neovascularization (-2.04+/-1.57% of total corneal area; P = 0.0047), whereas the low dose tended to stabilize it (0.07+/-2.94%; P = 0.2088) compared with placebo (0.89+/-2.15%), where corneal neovascularization progressed in all patients. There was no apparent benefit to the higher dose (1.60+/-7.63%). CONCLUSIONS The interim results of this phase II study suggest that GS-101 eye drops at an optimal dose of 86 microg/day are an effective and noninvasive approach specifically to inhibit and regress active corneal angiogenesis, a major risk factor for corneal graft transplantation and graft rejection. Safety concerns were not detected. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Intravitreal Aflibercept for Macular Edema Secondary to Central Retinal Vein Occlusion: 18-Month Results of the Phase 3 GALILEO Study

PURPOSE To evaluate intravitreal aflibercept for treatment of macular edema secondary to central retinal vein occlusion (CRVO). DESIGN Randomized, double-masked, phase 3 study. METHODS A total of 177 patients with macular edema secondary to CRVO were randomized to receive 2 mg intravitreal aflibercept (n = 106) or sham (n = 71) every 4 weeks for 20 weeks. From weeks 24 to 48, patients were monitored every 4 weeks; the former group received intravitreal aflibercept as needed (PRN), and the sham group received sham. From weeks 52 to 76, patients were monitored every 8 weeks, and both groups received intravitreal aflibercept PRN. The primary endpoint (proportion of patients who gained ≥15 letters) was at week 24. This study reports exploratory outcomes at week 76. RESULTS The proportion of patients who gained ≥15 letters in the intravitreal aflibercept and sham groups was 60.2% vs 22.1% at week 24 (patients discontinued before week 24 were considered nonresponders; P < .0001), 60.2% vs 32.4% at week 52 (last observation carried forward, P < .001), and 57.3% vs 29.4% at week 76 (last observation carried forward; P < .001). Mean μm change from baseline central retinal thickness was -448.6 vs -169.3 at week 24 (P < .0001), -423.5 vs -219.3 at week 52 (P < .0001), and -389.4 vs -306.4 at week 76 (P = .1122). Over 76 weeks, the most common ocular serious adverse event in the intravitreal aflibercept group was macular edema (3.8%). CONCLUSIONS The visual and anatomic improvements seen after fixed, monthly dosing at week 24 were largely maintained when treatment intervals were extended. Patients with macular edema following CRVO benefited from early treatment with intravitreal aflibercept.

Recurrent corneal erosion syndrome.

Recurrent corneal erosion syndrome is a chronic relapsing disease of the corneal epithelium characterized by repeated episodes of sudden onset of pain usually at night or upon first awakening, accompanied by redness, photophobia, and watering of the eyes. Individual episodes may vary in severity and duration. These symptoms are related to corneal deepithelialization in an area in which the epithelium is weakly adhered. It is a frustrating disorder for both the patient and the physician. In the majority of cases, the acute episode is managed by patching, and cycloplegic and topical antibiotic ointment, with prophylactic application of gels during daytime and ointment at night to prevent further erosion. In a minority of cases these measures are insufficient and may need alternative treatment modalities including therapeutic contact lens wear, anterior stromal puncture, superficial keratectomy, Nd:YAG, and most effectively, excimer laser therapy (phototherapeutic keratectomy).

The IC3D Classification of the Corneal Dystrophies

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 .

Salzmann's nodular degeneration of the cornea: a review and case series.

Salzmanns nodular degeneration is a rare, noninflammatory, slowly progressive, degenerative condition. Bluish-white nodules raised above the surface of the cornea characterize it. It has usually developed in corneas with a history of phlyctenulosis, trachoma, vernal keratoconjunctivitis, measles, scarlet fever, and various other viral diseases. However, today the majority of cases have been seen without recognized previous keratitis. It is composed of dense irregularly arranged collagen tissue with hyalinization between epithelium and Bowmans layer or beyond. Manual removal, phototherapeutic keratectomy (PTK) with or without the use of topical mitomycin-C, lamellar or penetrating keratoplasty have been used in the treatment of this disease. Salzmanns nodular degeneration does not seem to consist of one clinical entity. In some cases, elevated and pannus-like tissue can be separated easily from the corneal surface leaving Bowmans layer almost untouched. In these eyes, subsequent PTK may be necessary to smooth the surface. Recurrences are rare in these eyes. In contrast, some eyes (often with major peripheral vascularization) are left with deep defects in Bowmans layer and superficial stroma after difficult mechanical removal of nodules. In these eyes, multiple masking/laser ablation procedures are mandatory to acquire a homogenous surface. In our experience, the required laser ablation depth is significantly greater and the best-corrected visual acuity to be expected is reduced in contrast to the eyes with easy removal of the nodules. In these eyes recurrences seem to occur more frequently after treatment. Of 35 eyes documented to have Salzmanns nodular degeneration during the last 15 years in our department, 22 needed PTK treatment. Visual acuity increased from 0.4 to 0.7 on average. As a routine, laser ablation should be combined with previous conventional removal of nodules and excessive pannus tissue. By doing so, lamellar and penetrating keratoplasty techniques are hardly ever required in those eyes.