Treatment of type I ROP with intravitreal bevacizumab or laser photocoagulation according to retinal zone.

AIMS: To investigate the outcome of intravitreal bevacizumab (IVB) compared with laser photocoagulation in type I retinopathy of prematurity (ROP). METHODS: Case records of 54 consecutive very low birth weight (VLBW) infants with type I ROP (posterior ROP, n=33; peripheral zone II, n=21) who were treated either with IVB (n=37) or laser photocoagulation (n=17) between 2011 and 2015 were retrospectively evaluated. RESULTS: Patients with posterior ROP displayed significantly faster regression of active ROP within 12 days (range 9-15 days) if treated with IVB compared with laser photocoagulation, where active ROP regressed within 57 days (range 28-63 days) (p>0.001). No difference was observed in peripheral zone II.Five of seven patients (12%) who developed a recurrence in both eyes after IVB required additional laser photocoagulation within a mean of 12.7 weeks (11.3-15.6 weeks) after the previous treatment. After laser photocoagulation one patient with posterior ROP developed macular dragging and another patient developed a temporary exudative retinal detachment in both eyes. 12 months after treatment the spherical equivalent was not statistically significant different between IVB and laser photocoagulation in posterior ROP patients. However, IVB lead to a significant lower spherical equivalent in infants with posterior ROP (+0.37 dioptres, range -0.5 to +1.88 dioptres) compared with peripheral zone II (+3.0 dioptres range +2.0 to +4.0 dioptres, p<0.001). CONCLUSIONS: IVB leads to faster regression of active ROP in infants with posterior ROP compared with laser photocoagulation. Spherical equivalent after 12 months was comparable in those treated with IVB and laser photocoagulation, but it was significantly lower in posterior ROP than in peripheral zone II.

[Comparison of hang-back recession and conventional recession for correction of exotropia]. / Vergleich der Rücklagerung an Schlingen mit der konventionellen Rücklagerung zur Exotropiekorrektur.

BACKGROUND AND OBJECTIVE: Weakening of the lateral rectus muscle to correct exotropia can be achieved by using a conventional or a hang-back recession. This study was conducted to compare the results of these techniques and to analyze the dose-response curve and complication rates. STUDY DESIGN AND METHODS: Patients who underwent a lateral rectus muscle recession for exotropia were included in this retrospective study. The recession was performed conventionally with direct scleral fixation at the desired point or with a hang-back recession, each combined with a plication of the ipsilateral medial rectus muscle. The study analyzed ocular alignment and motility preoperatively as well as 1 day and 3 months postoperatively. Intraoperative and postoperative complications were compared. RESULTS: A total of 50 patients (age 4-75 years) met the inclusion criteria for this study. A conventional recession of the lateral rectus muscle was performed in 30 patients and a hang-back recession in 20. Preoperative ocular alignment with distance fixation was - 33.8 ± 14.4 prism diopters (PD) in the conventional group and - 30.6 ± 11.8 PD (mean ± standard deviation) in the hang-back group (where negative values constitute exotropia and positive values are esotropia). Preoperative ocular alignment with near fixation was - 40 ± 15.2 PD and - 36 ± 14.7 PD for conventional and hang-back recession, respectively. Ocular alignment with distance fixation 3 months postoperatively was - 10 ± 14.1 PD in the conventional group and - 11.1 ± 13.2 PD in the hang-back group and with near fixation it was - 15.4 ± 13.9 PD and - 11.5 ± 13.9 PD, respectively. In the conventional group 1 mm of combined surgery corrected 2.03 ± 0.88 PD (- 0.31-4.15 PD/mm) of exotropia with distance fixation and 2.13 ± 0.87 PD (0.89-3.85 PD/mm) with near fixation. In the hang-back group, it corrected 1.83 ± 0.89 PD (0.42-2.95 PD/mm) and 2.32 ± 1.25 PD (0.17-4.76 PD/mm), respectively. Differences between groups were not statistically significant. Intraoperative complications, such as scleral perforation were not observed. Postoperative complications, particularly slipped or lost muscles or induced vertical strabismus were not documented in either group. CONCLUSION: The hang-back recession is an effective and safe alternative to conventional recession of the lateral rectus muscle for exotropia. Larger studies with longer follow-up would be desirable to prospectively compare these two techniques.

[Intermittent Exotropia]. / Intermittierende Exotropie.

Intermittent exotropia (IXT) is a congenital form of divergent strabismus. Its incidence is estimated to be 32 per 100 000. Most often, IXT is first noted in early childhood when intermittently manifest outward deviation of the eyes is seen. Patients with IXT can control the deviation and keep the eyes aligned; this ability can be measured with "control scores". Complications such as amblyopia and loss of binocular functions are rare but should be looked for and need to be avoided. IXT can have a negative impact on quality of life. Conservative treatment includes the correction of refractive errors, (alternating) occlusion, over-minus lenses and orthoptic exercises. By injecting an extraocular muscle with botulinum toxin (to weaken its function) or with bupivacaine (to strengthen its function), IXT can be treated pharmacologically. Diagnostic occlusion and prism adaptation are strategies to uncover the true (largest) angle. Eye muscle surgery aims at eliminating the condition, but recurrences are common. The literature on large, randomized prospective trials for IXT is scarce. However, there are trials underway in the United Kingdom and in North America to better understand the natural course of IXT and to determine the most appropriate therapeutic approach.

Ultraviolet and middle wavelength sensitive cone responses in the electroretinogram (ERG) of normal and Rpe65 -/- mice.

Ultra-violet (UV) and middle wavelength sensitive (M) cone responses were identified in the ERG of normal and Rpe65 -/- mice using chromatic flashes and selective chromatic adaptation. In normal mice, the UV-cone response was as large as, or larger, in the presence of a bright yellow adapting light than it is in the presence of a dim white light. The M-cone response became undetectable in the presence of the yellow adapting light. Yellow adapting light initially reduced the UV response, but it recovered in 8-10 min. The M-cone response did not recover. UV-cone responses were undetectable in Rpe65 -/- mice. The M-cone response of young Rpe65 -/- mice was almost as large as in normal mice. A yellow adapting light only diminished this M-cone response. With age, the M-cone response further decreased in Rpe -/- mice. We show a pronounced loss of UV-cone function in Rpe65 -/- mice, which may be related to a defect UV-cones share with rods. The M-cone function is also affected already in young Rpe65 -/- mice. The transient effect of a yellow adapting light on the UV-cone response of normal mice is suggested to be neural, because it disappears during maintained light adaptation.

Isolation of human fetal cones.

PURPOSE: To describe a method for isolating a monolayer of human fetal cone photoreceptors and to compare their structure and ultrastructure before and after preparation. METHODS: Eyes from human fetuses (fetal week 20 to 24) were dissected and the neural retina of the developing fovea identified, cut out and placed on 10% gelatin. A VISX Star excimer laser was used to remove the inner retinal layers. The isolated cone monolayers were cultured for 18 hours and compared with untreated retinas by light microscopy and transmission electron microscopy. RESULTS: Excimer laser ablation removed the inner nuclear and ganglion cell layers leaving a monolayer of fetal cones. These cones survive in culture for at least 18 hours. The laser ablation disorganized the ultrastructure of the synaptic pedicles of these cones, left their plasma membranes intact. CONCLUSIONS: The developing central retina of human fetal eyes provides a source of fetal cones, which can be isolated from inner retinal cells using the excimer laser. Such a monolayer of human fetal cones may be useful for transplantation or biochemical studies.

In vivo studies of the gamma subunit of retinal cGMP-phophodiesterase with a substitution of tyrosine-84.

The inhibitory rod cGMP phosphodiesterase gamma subunit (PDEgamma) is a major component of the photoresponse and is required to support rod integrity. Pdeg(tm1)/Pdeg(tm1) mice (which lack PDEgamma owing to a targeted disruption of the Pdeg gene) suffer from a very rapid and severe photoreceptor degeneration. The Y84G (Tyr(84)-->Gly) allele of PDEgamma has previously been shown in experiments carried out in vitro to reduce the regulatory control of the PDE catalytic core (PDEalphabeta) exerted by the wild-type gamma subunit. To determine the effects of this mutation on in vivo function, the murine opsin promoter was used to direct expression to the photoreceptors of +/Pdeg(tm1) mice of a mutant Y84G and a wild-type PDEgamma control transgene. The transgenic mice were crossed with Pdeg(tm1)/Pdeg(tm1) mice to generate animals able to synthesize only the transgenic PDEgamma. Our results showed that wild-type PDEgamma and Y84G transgenes could complement the Pdeg(tm1)/Pdeg(tm1) mutant for photoreceptor survival. The mutation caused a significant biochemical defect in PDE activation by transducin. However, the Y84G mutation did not fully eliminate the control of PDEgamma on the PDE catalytic core in vivo; the expression of the mutant subunit was associated with only a 10-fold reduction in the amplitude of the a-wave and a 1.5-fold decrease in the b-wave of the corneal electroretinogram. Unexpectedly, the mutation caused a much 'milder' phenotype in vivo than was predicted from the biochemical assays in vitro.

A point mutation (W70A) in the rod PDE-gamma gene desensitizing and delaying murine rod photoreceptors.

PURPOSE: To examine the corneal electroretinogram (ERG) of transgenic mice (W70A mice) carrying a point mutation (W70A) in the gene encoding for the gamma-subunit of rod cGMP phosphodiesterase (PDEgamma). METHODS: The ERG of W70A mice was compared with that of normal mice. Cone responses were separated from rod responses by light adaptation, whereas rod sensitivity was assessed by threshold stimulation with dim light. Spectral sensitivity curves of the ERG were obtained using a constant response criterion. RESULTS: The ERG of the W70A mouse has a desensitized, delayed rod b-wave at threshold, and a prolonged rod b-wave at higher flash intensities. The a-wave is absent even at maximal stimulation. The cone ERG of the W70A mouse is indistinguishable from that of normal mice. The spectral sensitivity of the W70A mouse is maximal in the UV spectrum, in contrast to the normal mouse, which is most sensitive in the green region of the spectrum. This supports the interpretation of the results as normal cone and abnormal rod function in the W70A mouse. CONCLUSIONS: The W70A mouse represents new model of stationary nyctalopia that can be recognized by its unusual ERG features.

Impaired retinal function and vitamin A availability in mice lacking retinol-binding protein.

Retinol-binding protein (RBP) is the sole specific transport protein for retinol (vitamin A) in the circulation, and its single known function is to deliver retinol to tissues. Within tissues, retinol is activated to retinoic acid, which binds to nuclear receptors to regulate transcription of >300 diverse target genes. In the eye, retinol is also activated to 11-cis-retinal, the visual chromophore. We generated RBP knockout mice (RBP(-/-)) by gene targeting. These mice have several phenotypes. Although viable and fertile, they have reduced blood retinol levels and markedly impaired retinal function during the first months of life. The impairment is not due to developmental retinal defect. Given a vitamin A-sufficient diet, the RBP(-/-) mice acquire normal vision by 5 months of age even though blood retinol levels remain low. Deprived of dietary vitamin A, vision remains abnormal and blood retinol declines to undetectable levels. Another striking phenotype of the mutant mice is their abnormal retinol metabolism. The RBP(-/-) mice can acquire hepatic retinol stores, but these cannot be mobilized. Thus, their vitamin A status is extremely tenuous and dependent on a regular vitamin A intake. Unlike wild-type mice, serum retinol levels in adult RBP(-/-) animals become undetectable after only a week on a vitamin A-deficient diet and their retinal function rapidly deteriorates. Thus RBP is needed for normal vision in young animals and for retinol mobilization in times of insufficient dietary intake, but is otherwise dispensable for the delivery of retinol to tissues.

Histology after lamellar keratoplasty and corneal excimer laser ablation.

PURPOSE: To correlate clinical and histological findings after lamellar keratoplasty, phototherapeutic keratectomy, and application of a donor lenticule on a human cornea. METHODS: A cornea was obtained during penetrating keratoplasty. The specimen was fixated, dehydrated and embedded in Epon resin. The tissue was cut in 0.5-microm-thick semi-thin sections, stained with toluidine blue, and studied with light microscopy. RESULTS: The central part of the photoablated cornea, which was covered by the donor lenticule, did not differ from a normal cornea. Peripherally, a hazy ring was found clinically. Histology showed an irregular epithelium. Where it was thickened, the epithelium was hyperplastic and showed an increased number of cell layers. In the hazy region, Bowman's layer was absent, indicating that the donor lenticule did not cover this part of the photokeratectomized cornea. The anterior-most part of the corneal stroma was vacuolized and contained amorphous extracellular material; swollen keratocytes were present in this region. Beneath this layer, collagen lamellae were wavy and interwoven and keratocytes were increased in number, appeared swollen, and some had assumed an atypical shape. Peripheral to the haze, the cornea was clear. Histologically, the epithelium was irregular and hyperplastic, Bowman's layer was absent, and stromal collagen lamellae were abnormally organized, but no vacuolization was found. CONCLUSIONS: The formation of haze after excimer laser photokeratectomy can be minimized if the ablated stroma is covered by a corneal lenticule.

Comparison of objective and subjective refraction before and after laser in situ keratomileusis.

PURPOSE: To compare the accuracy and reliability of objective and subjective refractions before and after laser in situ keratomileusis (LASIK) for myopia, hyperopia, and astigmatism. SETTING: Augenchirurgie und Laserzentrum Hochrum, Innsbruck, Austria. METHODS: In this prospective study, the objective refraction obtained with the Nidek AR-K 900 autorefractor was compared with the subjective refraction in 159 eyes (125 with myopia and 34 with hyperopia) operated on with 2 different lasers. Refractions were done before and 6 months after LASIK. RESULTS: Preoperatively, the objective and subjective refractions correlated better in eyes with low myopia than in those with high myopia (P < .01). Postoperatively, objective refraction was less accurate and reliable than preoperatively. The difference between the objective and subjective spherical refractions was statistically significant (P < .0001) after LASIK in eyes with hyperopia. The correlation between the objective and subjective cylindrical refractions was stronger preoperatively. Especially after LASIK for hyperopia, the objective refraction did not reliably assess the magnitude and axis of the cylinder. The preoperative refractive error did not significantly affect the preoperative and postoperative difference between the objective and subjective refractions or the change between the preoperative and postoperative mean differences. The type of excimer laser used significantly affected the difference between the objective and subjective refractions. CONCLUSIONS: Especially after LASIK for hyperopia, the objective refraction determined with the Nidek AR-K 900 autorefractor delivered erroneous results, which have implications for postoperative care and preoperative measurements for ocular surgery such as enhancement procedures or cataract surgery.

[Laser in situ keratomileusis (LASIK) for correction of myopia and astigmatism]. / Laser-in-situ-Keratomileusis (LASIK) zur Myopie- und Astigmatismuskorrektur.

PATIENTS AND METHODS: In order to better define the potential advantages and risks of laser in situ keratomileusis (LASIK), we designed a prospective study including 73 eyes. RESULTS: After 6 months, 62 eyes were examined. Myopia was corrected from -6.10 +/- 3.12 (mean +/- standard deviation) to +0.04 +/- 0.66 D, with 54 eyes (87.1%) being within +/- 1.00 D of emmetropia. Astigmatism was corrected from -1.07 +/- 1.02 to -0.32 +/- 0.89 D. Uncorrected visual acuity was 0.5 or better in 59 eyes (95.2%) and 1.0 or better in 27 eyes (43.5%) 6 months postoperatively. More than one line in best-corrected visual acuity was lost by 6 eyes (9.7%), with most of these eyes being highly myopic. There was no change or a gain in lines in best corrected visual acuity in 42 eyes (66.1%). Intraoperative complications arose in two eyes (2.7%); in one eye, visual acuity was temporarily decreased. More treatments were performed in 7 eyes (9.6%). Postoperatively, no haze, scars or central islands were detected. Patient satisfaction after LASIK was high: 97.3% were pleased or very pleased with the result. CONCLUSIONS: In conclusion, LASIK is effective in the correction of myopia and myopic astigmatism. Although complications more frequently occurred in the correction of higher refractive errors, LASIK seems to be relatively safe compared with other refractive methods.

Laser in situ keratomileusis for myopia and myopic astigmatism.

PURPOSE: To evaluate the precision and safety of myopia and astigmatism correction using laser in situ keratomileusis (LASIK). SETTING: Augenchirurgie und Laserzentrum Hoch-Rum (Sanatorium der Kreuzsch-western), Innsbruck, Austria. METHODS: In this prospective study, LASIK was performed on 66 eyes of 39 patients with myopia ranging from 1.50 to 16.00 diopters (D). Astigmatism, ranging from -0.00 to -3.00 D, was treated simultaneously. Surgery was performed with the Chiron Keracor 117 excimer laser and the Chiron Automated Corneal Shaper microkeratome. During the 6 month follow-up, manifest refraction as well as best corrected and uncorrected visual acuities were measured; corneal topographies were produced and slitlamp biomicroscopy was performed. Changes in visual acuity and corneal topography were evaluated. RESULTS: After 6 months, mean myopia had decreased from 6.78 D +/- 3.48 (SD) to 0.40 +/- 0.98 D. Fifty-one of 63 eyes (81.0%) were within +/- 1.00 D of spherical emmetropia and 61 of 63 (96.8%) within +/- 1.00 D of cylindrical emmetropia. Uncorrected visual acuity improved in all eyes; it was 20/40 or better in 82.5% 6 months postoperatively. Best corrected visual acuity did not change in most eyes; 9.5% lost two or more Snellen lines. No central islands or corneal scars were detected postoperatively. Haze was noted in only 6 eyes (9.1%); it was transient and less than grade 1. No sight-threatening complications occurred intraoperatively. CONCLUSION: Laser in situ keratomileusis was an exact and predictable procedure for correcting low, moderate, and high myopia and myopic astigmatism.

Laser in situ keratomileusis after automated lamellar keratoplasty and penetrating keratoplasty.

We present three patients who had laser in situ keratomileusis (LASIK) after corneal surgery as follow: 15 months after automated lamellar keratoplasty (ALK) for hyperopia, 6 months after ALK for hyperopia, and 2 years after penetrating keratoplasty (PKP). Although the first case was uneventful, intraoperative complications arose in the second case because the connection of the ALK-related flap to its stromal bed was insufficient. In the third case, the refractive error caused by PKP was corrected as shown by corneal topography and visual acuity measurement. In conclusion, LASIK after PKP can be considered a precise and safe procedure if 2 to 3 years pass between the procedures. An interval of 6 months between ALK and LASIK was too short, whereas 15 months after ALK for hyperopia, LASIK was performed without problems and delivered a good result.