Orthokeratology and Low-Intensity Laser Therapy for Slowing the Progression of Myopia in Children.

Orthokeratology (OK) is widely used to slow the progression of myopia. Low-level laser therapy (LLLT) provides sufficient low energy to change the cellular function. This research is aimed at verifying the hypothesis that LLLT treatment could control myopia progression and comparing the abilities of OK lenses and LLLT to control the refractive error of myopia. Eighty-one children (81 eyes) who wore OK lenses, 74 children (74 eyes) who underwent LLLT treatment, and 74 children (74 eyes) who wore single-vision distance spectacles for 6 months were included. Changes in axial length (AL) were 0.23 ± 0.06 mm for children wearing spectacles, 0.06 ± 0.15 mm for children wearing OK lens, and -0.06 ± 0.15 mm for children treated with LLLT for 6 months. Changes in subfoveal choroidal thickness (SFChT) observed at the 6-month examination were -16.84 ± 7.85 µm, 14.98 ± 22.50 µm, and 35.30 ± 31.75 µm for the control group, OK group, and LLLT group, respectively. Increases in AL at 1 month and 6 months were significantly associated with age at LLLT treatment. Changes in AL were significantly correlated with the baseline spherical equivalent refraction (SER) and baseline AL in the OK and LLLT groups. Increases in SFChT at 1 month and 6 months were positively associated with age at enrolment for children wearing OK lens. At 6 months, axial elongation had decelerated in OK lens-wearers and LLLT-treated children. Slightly better myopia control was observed with LLLT treatment than with overnight OK lens-wearing. Evaluations of age, SER, and AL can enhance screening for high-risk myopia, improve the myopia prognosis, and help determine suitable control methods yielding the most benefits.

In vivo Structural Assessments of Ocular Disease in Rodent Models using Optical Coherence Tomography.

Spectral-domain optical coherence tomography (SD-OCT) is useful for visualizing retinal and ocular structures in vivo. In research, SD-OCT is a valuable tool to evaluate and characterize changes in a variety of retinal and ocular disease and injury models. In light induced retinal degeneration models, SD-OCT can be used to track thinning of the photoreceptor layer over time. In glaucoma models, SD-OCT can be used to monitor decreased retinal nerve fiber layer and total retinal thickness and to observe optic nerve cupping after inducing ocular hypertension. In diabetic rodents, SD-OCT has helped researchers observe decreased total retinal thickness as well as decreased thickness of specific retinal layers, particularly the retinal nerve fiber layer with disease progression. In mouse models of myopia, SD-OCT can be used to evaluate axial parameters, such as axial length changes. Advantages of SD-OCT include in vivo imaging of ocular structures, the ability to quantitatively track changes in ocular dimensions over time, and its rapid scanning speed and high resolution. Here, we detail the methods of SD-OCT and show examples of its use in our laboratory in models of retinal degeneration, glaucoma, diabetic retinopathy, and myopia. Methods include anesthesia, SD-OCT imaging, and processing of the images for thickness measurements.

Disrupted potassium ion homeostasis in ciliary muscle in negative lens-induced myopia in Guinea pigs.

Myopia is a main cause of preventable or treatable visual impairment, it has become a major public health issue due to its increasingly high prevalence worldwide. Currently, it is confirmed that the development of myopia is associated with the disorders of accommodation. As a dominant factor for accommodation, ciliary muscle contraction/relaxation can regulate the physiological state of the lens and play a crucial role in the development of myopia. To investigate the relationship between myopia and ciliary muscle, the guinea pigs were randomly divided into a normal control (NC) group and a negative lens-induced myopia (LIM) group, and the animals in each group were further randomly assigned into 2-week (n = 18) and 4-week (n = 21) subgroups in accordance with the duration of myopic induction of 2 and 4 weeks, respectively. In the present study, right eyes of the animals in LIM group were covered with -6.0 D lenses to induce myopia. Next, we performed the haematoxylin and eosin (H&E) staining to observe the pathological change of ciliary muscle, determined the contents of adenosine triphosphate (ATP) and lactate acid (LA), and measured the Na+/K+-ATPase expression and activity in ciliary muscles in both NC and LIM groups. Moreover, we also analyzed the potassium ion (K+) flux in ciliary muscles from 4-week NC and LIM guinea pigs. As a result, we found that the arrangements of ciliary muscles in LIM guinea pigs were broken, dissolved or disorganized; the content of ATP decreased, whereas the content of LA increased in ciliary muscles from LIM guinea pigs. Monitoring of K+ flux in ciliary muscles from LIM guinea pigs demonstrated myopia-triggered K+ influx. Moreover, we also noted a decreased expression of Na+/K+-ATPase (Atp1a1) at both mRNA and protein levels and reduced activity in ciliary muscles from LIM guinea pigs. Overall, our results will facilitate the understanding of the mechanism associated with inhibitory Na+/K+-ATPase in lens-induced myopia and which consequently lead to the disorder of microenvironment within ciliary muscles from LIM guinea pigs, paving the way for a promising adjuvant approach in treating myopia in clinical practice.

Estimation of the Minimum Effective Dose of Dietary Supplement Crocetin for Prevention of Myopia Progression in Mice.

The natural carotenoid crocetin has been reported to suppress phenotypes of an experimental myopia model in mice. We investigated the minimum effective dose to prevent myopia progression in a murine model. Three-week-old male mice (C57B6/J) were equipped with a -30 diopter (D) lens to induce myopia, and fed with normal chow, 0.0003%, or 0.001% of crocetin-containing chow. Changes in refractive errors and axial lengths (AL) were evaluated after three weeks. Pharmacokinetics of crocetin in the plasma and the eyeballs of mice was evaluated with specific high sensitivity quantitative analysis using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine the minimum effective dosage. A concentration of 0.001% of crocetin-containing chow showed a significant (p < 0.001) suppressive effect against both refractive and AL changes in the murine model. Meanwhile, there was no significant difference of AL change between the 0.0003% and the normal chow groups. The concentration of crocetin in the plasma and the eyeballs from mice fed with 0.001% crocetin-containing chow was significantly higher than control and 0.0003% crocetin-containing chow. In conclusion, we suggest 0.001% of crocetin-containing extract is the minimum effective dose showing a significant suppressive effect against both refractive and AL changes in the murine model.

Transepithelial photorefractive intrastromal corneal crosslinking versus photorefractive keratectomy in low myopia.

PURPOSE: To compare the outcomes of transepithelial photorefractive intrastromal corneal crosslinking (CXL) and photorefractive keratectomy (PRK) in eyes with low myopia. SETTING: Purpan Hospital, Toulouse, France. DESIGN: Prospective case series. METHODS: Myopic patients with a manifest refraction spherical equivalent (MRSE) of -1.00 to -2.50 diopters (D) and a cylindrical component of plano to -0.75 D were included. The dominant eye had PRK (PRK eyes). The nondominant eye had transepithelial photorefractive intrastromal CXL with riboflavin (ParaCel Part 1 and 2), 30 mW/cm2 pulsed ultraviolet-A irradiation centered on the pupil (Mosaic System) for 16 minutes and 40 seconds, and a supplemental oxygen delivery mask (CXL eyes). The primary outcome measure was the change in the MRSE. Other outcome measures were the uncorrected (UDVA) and corrected (CDVA) distance visual acuities, mean keratometry, and endothelial cell count (ECC) over a 6-month follow-up. Adverse events were assessed. RESULTS: Nineteen patients were included. By 6 months, the mean MRSE had decreased by 0.72 D ± 0.42 (SD) in CXL eyes and by 1.35 ± 0.46 D in PRK eyes (P < .001). The mean change in UDVA was -0.35 ± 0.21 logarithm of the minimum angle of resolution (logMAR) in CXL eyes and -0.66 ± 0.19 logMAR in PRK eyes (P < .001). No complications were reported. The change in the ECC and CDVA was not statistically significant. CONCLUSIONS: Photorefractive keratectomy provided better visual and refractive outcomes than transepithelial photorefractive intrastromal CXL. Transepithelial photorefractive intrastromal CXL, however, showed the potential refractive effect of CXL but with a limited magnitude of myopic correction.

Changes in dopamine and ZENK during suppression of myopia in chicks by intense illuminance.

High ambient illuminances have been found to slow the development of deprivation myopia in several animal models. Almost complete inhibition of myopia was observed in chickens when intermittent episodes of high illuminance were alternated with standard office illuminance (50% duty cycle, alternate periods of 1 min 15,000 lux and 1 min 500 lux, continued for 10 h per day), or when illuminances were increased to 40,000 lux. Since the mechanisms by which bright light suppresses myopia are poorly understood, we have studied the roles of two well-established signaling molecules in myopia, dopamine and ZENK, in the chicken. In line with previous studies, we found that retinal dopamine release (as reflected by vitreal DOPAC content) was severely reduced during development of deprivation myopia. We found that illuminance of 15,000 lux, provided by quartz-halogen lamps, partially rescued the drop in retinal dopamine release. The finding is in line with the assumption that dopamine is involved in the light-induced inhibition of myopia. No differences in vitreal DOPAC were found when bright light was provided continuously or with 1:1 min alternating exposure with 500 lux. As previously described by others, wearing diffusers suppressed the expression of ZENK protein in glucagonergic amacrine cells (GACs) but neither continuous nor 1:1 min alternating bright to normal light could rescue the suppression of ZENK in GACs. While it is well known that light increases global retinal ZENK mRNA and protein levels, the changes of ZENK protein induced specifically in GACs by diffuser wear appear independent of light levels.

Autofluorescence imaging and spectral-domain optical coherence tomography in incomplete congenital stationary night blindness and comparison with retinitis pigmentosa.

PURPOSE: To test the hypothesis that the evaluation of retinal structure can have diagnostic value in differentiating between incomplete congenital stationary night blindness (CSNB2) and retinitis pigmentosa (RP). To compare retinal thickness differences between patients with CSNB2 and myopic controls. DESIGN: Prospective cross-sectional study. METHODS: Ten eyes of 5 patients diagnosed with CSNB2 (4 X-linked recessive, 1 autosomal recessive) and 6 eyes of 3 patients with RP (2 autosomal dominant, 1 autosomal recessive) were evaluated with spectral-domain optical coherence tomography (SD OCT) and fundus autofluorescence (FAF). Diagnoses of CSNB2 and RP were confirmed by full-field electroretinography (ERG). Manual segmentation of retinal layers, aided by a computer program, was performed by 2 professional segmenters on SD OCT images of all CSNB2 patients and 4 age-similar, normal myopic controls. Seven patients were screened for mutations with congenital stationary night blindness and RP genotyping arrays. RESULTS: Patients with CSNB2 had specific findings on SD OCT and FAF that were distinct from those found in RP. CSNB2 patients showed qualitatively normal SD OCT results with preserved photoreceptor inner segment/outer segment junction, whereas this junction was lost in RP patients. In addition, CSNB2 patients had normal FAF images, whereas patients with RP demonstrated a ring of increased autofluorescence around the macula. On SD OCT segmentation, the inner and outer retinal layers of both X-linked recessive and autosomal recessive CSNB2 patients were thinner compared with those of normal myopic controls, with means generally outside of normal 95% confidence intervals. The only layers that demonstrated similar thickness between CSNB2 patients and the controls were the retinal nerve fiber layer and, temporal to the fovea, the combined outer segment layer and retinal pigment epithelium. A proband and his 2 affected brothers from a family segregating X-linked recessive CSNB2 had a mutation, p.R614X, in the gene encoding calcium channel, α 1F subunit. CONCLUSIONS: CSNB2 patients (X-linked recessive and autosomal recessive) had significantly thinner retinas than myopic controls. However, they demonstrated qualitatively normal SD OCT and FAF images, and therefore can be differentiated from RP patients with these techniques. Although ERG testing remains the gold standard for the diagnosis of these conditions, FAF and SD OCT systems are more widely available to community ophthalmologists, offer shorter acquisition times, and, unlike ERG, can be performed on the same day as the initial clinic visit. Therefore, as a supplement to ERG and genetic testing, we advocate the use of FAF and SD OCT in the examination of patients with CSNB2 and RP.

[Efficacy of intravitreal injections of ranibizumab compared to visudyne phototherapy in myopic choroidal neovascularization associated with high myopia]. / Comparaison du traitement par injections intravitréennes de ranibizumab à la photothérapie dynamique dans la néovascularisation choroïdienne compliquant la myopie forte.

INTRODUCTION: Myopic choroidal neovascularization (CNV) is the first cause of CNV in young patients. The aim of this study was to compare the efficacy of intravitreal injections (IVT) of ranibizumab with photodynamic therapy (PDT) in this indication. PATIENTS AND METHODS: Retrospective comparative study analyzing the visual acuity (VA) outcomes of CNV myopic patients treated with either IVT or PDT. RESULTS: Twenty-seven eyes of 25 patients were treated with PDT (group 1) and 18 eyes of 17 patients were treated with IVT of ranibizumab (group 2). Demographic data were similar in the two groups. The median initial VA was 20/80 for group 1 and 20/160 for group 2 (P=0.37). At 1 year, the median VA was 20/80 for group 1 (P=0.32) and 20/63 for group 2 (P=0.04). A significant improvement in VA was observed in 23.1% and in 27.3% of cases in groups 1 and 2, respectively (P=0.53). A significant VA worsening was observed in 34.6% of cases in group 1 and in 9.1% of cases in group 2 (P=0.21). CONCLUSION: IVT of ranibizumab compared to PDT treatment showed greater efficacy in this study.

Corneal ablation depth readout of the MEL 80 excimer laser compared to Artemis three-dimensional very high-frequency digital ultrasound stromal measurements.

PURPOSE: To evaluate the accuracy of the ablation depth readout for the MEL 80 excimer laser (Carl Zeiss Meditec). METHODS: Artemis 1 very high-frequency digital ultrasound measurements were obtained before and at least 3 months after LASIK in 121 eyes (65 patients). The Artemis-measured ablation depth was calculated as the maximum difference in stromal thickness before and after treatment. Laser in situ keratomileusis was performed using the MEL 80 excimer laser and the Hansatome microkeratome (Bausch & Lomb). The Aberration Smart Ablation profile was used in 56 eyes and the Tissue Saving Ablation profile was used in 65 eyes. All ablations were centered on the corneal vertex. Comparative statistics and linear regression analysis were performed between the laser readout ablation depth and Artemis-measured ablation depth. RESULTS: The mean maximum myopic meridian was -6.66±2.40 diopters (D) (range: -1.50 to -10.00 D) for Aberration Smart Ablation-treated eyes and -6.50±2.56 D (range: -1.34 to -11.50 D) for Tissue Saving Ablation-treated eyes. The MEL 80 readout was found to overestimate the Artemis-measured ablation depth by 20±12 µm for Aberration Smart Ablation and by 21±12 µm for Tissue Saving Ablation profiles. CONCLUSIONS: The accuracy of ablation depth measurement was improved by using the Artemis stromal thickness profile measurements before and after surgery to exclude epithelial changes. The MEL 80 readout was found to overestimate the achieved ablation depth. The linear regression equations could be used by MEL 80 users to adjust the ablation depth for predicted residual stromal thickness calculations without increasing the risk of ectasia due to excessive keratectomy depth as long as a suitable flap thickness bias is included.

Effects of unilateral topical atropine on binocular pupil responses and eye growth in mice.

PURPOSE: Studies on drugs selected to target myopia development often use the vehicle-treated fellow eye as a control. However, it is not clear how much of the drug reaches the fellow eye, rendering it a potentially invalid control. Therefore, in this study, pupil responses were used to probe the effects of atropine in both eyes in mice, after unilateral topical application. In a second experiment, interocular differences in refractive development and axial eye growth were studied while atropine was applied daily to one eye. METHODS: In 20 C57BL/6 (B6) wildtype mice, a single drop of 1% atropine solution was instilled into one eye. Mice were gently restrained by holding their necks while video image processing software detected the pupil and measured its diameter at a sampling rate of 30 Hz. A bright green LED, attached to the photoretinoscope of the video camera, was flashed. Pupil responses were quantified daily over a period of 2 weeks. In another group of 24 mice, one drop of 1% atropine was applied daily for 28 days. Axial length was measured pre- and post-treatment, using low coherence interferometry (the Zeiss AC-Master). Refractive development was measured by infrared photorefraction. RESULTS: Similar to previous findings with the same device, untreated eyes displayed a pupil constriction of 24.84+/-1.73% upon stimulation with the green LED. A single drop of 1% atropine caused complete suppression with no significant recovery over the whole observation period of two weeks. The responses in the fellow eye were temporarily reduced to about 75% and then recovered towards baseline. After daily atropine application, there was significant reduction in axial length of the eyes, relative to the saline-treated fellow eyes (3.234+/-0.186 versus 3.378+/-0.176 mm, n=24, p<0.01, paired t-test) and the refractions became more hyperopic/less myopic (+13.46+/-2.15 D versus +10.06+/-2.02 D, n=24, p<0.01). CONCLUSIONS: In line with previous findings, one drop of atropine solution caused a long lasting suppression of pupil responses in the mouse eye. New data show that the transfer to the fellow eye was limited, making interocular comparisons feasible. It is also new that topical atropine reduced axial eye growth even when mice had largely normal vision.

Corneal reshaping: is it a good alternative to refractive surgery?

PURPOSE OF REVIEW: To review current literature on overnight corneal reshaping and present this mode of vision correction in its current state. RECENT FINDINGS: Overnight corneal reshaping uses specially designed rigid gas-permeable contact lenses. It is effective in temporarily reducing or eliminating low to moderate myopia. This nonsurgical mode of vision correction allows for good unaided vision during waking hours. There are reports of young patients experiencing serious adverse events, particularly bacterial and Acanthamoeba keratitis while using these lenses, although incidence rates are unknown. SUMMARY: Overnight corneal reshaping is an alternative to refractive surgery and must continue to be studied and monitored to establish its safety.

Myopia: attempts to arrest progression.

Previous studies have evaluated the efficacy of several interventions to decrease the progression of myopia. These include devices that alter the perception of the visual environment and pharmacological treatments. There is no conclusive evidence thus far that alteration of the pattern of spectacle wear, bifocals, ocular hypotensives, or contact lenses retards the progression of myopia. Several randomised clinical trials have demonstrated that the rate of progression of myopia is lower in children given atropine eye drops than those given placebo. However, atropine is associated with short term side effects such as photophobia and possible long term adverse events including light induced retinal damage and cataract formation. Other more selective antimuscarinic agents such as pirenzipine are presently being evaluated. Further well conducted randomised clinical trials with large sample sizes and adequate follow up designed to evaluate treatments to retard the progression of myopia should be conducted, since the identification of an effective intervention may have a greater public health impact on the burden and morbidity from myopia than the few treatments currently available.

Altered globe dimensions of axial myopia as risk factors for penetrating ocular injury during peribulbar anaesthesia.

We measured the range of equatorial horizontal widths (EHW) in axially myopic eyes and identified the sites of staphyloma using B scan echography. One hundred eyes in 50 patients were studied. The axial lengths (ALs) were sorted into five groups of increasing severity of myopia. The group mean AL, group mean EHW and the ratio of EHW/AL was calculated for each range. The results suggest that the increase in the AL in an axially myopic eye is associated with an increase in the EHW. However, this increase in the group mean EHW is relatively small (2.3 mm) compared with the increase mean AL (8.2 mm) across the entire range. The ratio of EHW/AL decreased with an increase in the group mean AL. Therefore, the increase in EHW in an axially myopic eye is unlikely to be a significant risk factor for inadvertent ocular injury for peribulbar injections if a careful single medial canthal approach is used. There was high incidence of staphylomas in eyes with AL > 29 mm, most were inferior to the posterior pole of the globe, and there were none at the equator.

Optic disc morphology in myopic primary open-angle glaucoma.

OBJECTIVE: To evaluate the morphology of the optic disc in highly myopic eyes with primary open-angle glaucoma. METHODS: Color stereo optic disc photographs of 44 patients with primary open-angle glaucoma and a myopic refractive error exceeding -8 diopters were morphometrically examined and compared with disc photographs of 571 patients with primary open-angle glaucoma and a myopic refractive error of less than -8 diopters. RESULTS: In the highly myopic group, compared to the control group, the optic disc was significantly (P < 0.0001) larger, the disc shape was significantly (P < 0.0005) more elongated, and the optic cup depth was significantly (P < 0.0001) more shallow. The loss of neuroretinal rim was more concentric, and localized retinal nerve fiber layer defects were found significantly less frequently in the highly myopic group than in the control group. In the highly myopic group, zone beta of parapapillary atrophy was significantly (P < 0.0001) larger. CONCLUSION: The optic disc morphology in primary open-angle glaucoma differs significantly between highly myopic eyes and eyes with hyperopia or low to moderate myopia. The highly myopic eyes are characterized by secondary macro-discs with elongated shape, shallow and concentric disc cupping, large parapapillary atrophy, and low frequency of localized retinal nerve fiber layer defects. Glaucomatous optic nerve damage in highly myopic eyes, compared to eyes with a normal refractive error, is more diffuse than localized.

[The morphological justification for the use of collagenoplasty in progressive myopia]. / Morfologicheskoe obosnovanie primeneniia kollagenoplastiki pri progressiruiushchei blizorukosti.

A morphological study in 20 rabbits was performed in order to investigate the response of the eye tissues and the changes in the collagen spongious preparations implanted into the episcleral space. Aseptic inflammation developing in the episcleral space was local and did not have influence on the state of the retina and choroid. The collagen implants underwent lysis, resorption and were gradually replaced by the connective tissue with the development of the episcleral scar that increased the thickness of the sclera from 1.5 to 2.5-fold during 1-2 months. These results are the basis for the successful surgical correction of the high progressing myopia.

Optic pit versus glaucomatous cupping in a myopic patient.

A myopic patient with bilaterally deep cupping of her optic discs and an arcuate scotoma in the bjerrum area in the right eye and borderline IOP is presented. The problem of diagnosing a glaucomatous process in this patient is discussed.

Optic disc cupping and prematurity. Large cups as a possible low birth weight sequel.

In a previous ophthalmic study of ex-prematures around the age of 10 years it was accidentally found that cupping of the optic disc was significantly more pronounced in children of a low birth weight (less than 2000 g) than in full-term controls (Fledelius 1976). This was true for cup size (cup/disc diameter ratio) as well as depth (as indicated by a visible cribriform plate). The present analyses make up an extension of the above study, with additional calculations based on some of its data. Within the ex-prematures (n = 268) the cup size did not seem to be related to birth weight, sex, or visual acuity. Eyes with myopia of prematurity were not especially 'loaded' with large cups. For the whole sample (including the 187 full-term control there was a weak association between cup size and refraction (and axial eye length). Larger cups occurred relatively more often in myopic eyes. Possible mechanisms behind early changes in disc are discussed (astroglial hypothesis--distension of disc--loss of retinal nerve fibers). It is felt that this new observation--large disc cupping as a possible low birth weight sequel--has to be substantiated by further clinical evidence, as statistical type 1 error (mass significance) cannot be ruled out.