Functional and structural efficacy of a novel combinational therapy of aflibercept and timely focal/grid photocoagulation in diabetic macular oedema: do clinical study results compare favourably with a standard-of-care treated real-world population?

PURPOSE: To evaluate treatment efficacy in diabetic macular oedema (DME) comparing a study population receiving combined intravitreal vascular endothelial growth factor (VEGF) inhibition and focal/grid photocoagulation with a matched, real-world population receiving standard of care treatment. METHODS: In an exploratory study, we included 43 eyes from 32 patients from a previously published study as well as 46 eyes from 38 standard-of-care patients. The study population had received a loading dose of three monthly aflibercept injections followed by focal/grid photocoagulation and additional aflibercept pro re nata. Principal measurements at 12 months were numbers of intravitreal injections, best corrected visual acuity (BCVA) and central retinal thickness (CRT). RESULTS: At baseline, there were no differences between groups regarding age, sex, body mass index, haemoglobin A1 C, systolic pressure or type of diabetes, but the study population had a higher diastolic pressure (81.6 versus 72.1 mmHg, p = 0.03) and a lower duration of diabetes (12.3 versus 23.2 years, p = 0.03). At month 12, patients in the study group had a higher visual acuity (79.6 versus 74.3 ETDRS letters, p = 0.03), despite having received fewer aflibercept injections (4.4 versus 5.9, p < 0.01) with a higher likelihood of having only received the three mandatory injections in the loading phase (39.5% versus 13.0%, p = 0.01). CONCLUSION: In comparison to a matched, real-world DME-population, patients in combined treatment with intravitreal aflibercept and postloading focal/grid photocoagulation obtained a better functional outcome despite having received fewer intravitreal injections. Future randomized studies are needed to evaluate the long-term efficacy of this combined treatment regimen.

Central corneal sublayer pachymetry and biomechanical properties after refractive femtosecond lenticule extraction.

PURPOSE: To compare central corneal sublayer pachymetry and biomechanical properties after femtosecond lenticule extraction (FLEX) and small-incision lenticule extraction (SMILE). METHODS: A prospective, randomized, single-masked clinical trial of 35 patients treated for moderate to high myopia with FLEX in one eye and SMILE in the other. Anterior segment optical coherence tomography imaging (Heidelberg Spectralis; Heidelberg Engineering GmbH, Heidelberg, Germany) was used to measure central corneal thickness (CCT) and epithelial, flap/cap, and residual stromal bed thickness centrally. The Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY) was used to assess corneal hysteresis (CH) and corneal resistance factor (CRF). Patients were examined before and 6 months after surgery. RESULTS: Mean decrease in CCT was 105 µm in FLEX-treated eyes and 106 µm in SMILE-treated eyes (P = .70), which is equivalent to approximately 14 µm/diopters corrected. Mean central epithelial thickness increased 7 ± 6 µm in FLEX-treated eyes and 6 ± 5 µm in SMILE-treated eyes (P = .64). Achieved mean flap/cap thickness was 4 ± 6 µm from the expected thickness in FLEX-treated eyes and 4 ± 9 µm in SMILE-treated eyes (P = .37). CH was reduced 2.7 ± 1.3 mm Hg in FLEX-treated eyes and 3.3 ± 1.2 mm Hg in SMILE-treated eyes (P = .08). CRF was reduced 4.5 ± 1.2 mm Hg in FLEX-treated eyes and 4.6 ± 1.2 mm Hg in SMILE-treated eyes (P = .71). CH and CRF were highly correlated with CCT, but not patient age. CONCLUSIONS: In this paired-eye study, the flap-based FLEX and cap-based SMILE resulted in almost identical changes in central corneal sublayer pachymetry and biomechanical properties for moderate to high myopia 6 months after treatment.

Efficacy, safety, predictability, contrast sensitivity, and aberrations after femtosecond laser lenticule extraction.

PURPOSE: To compare femtosecond lenticule extraction and small-incision lenticule extraction to treat moderate to high myopia. SETTING: Department of Ophthalmology, Aarhus University Hospital, Aarhus, Denmark. DESIGN: Prospective clinical single-masked paired-eye study. METHODS: An intrastromal lenticule was cut by a femtosecond laser and manually extracted. In femtosecond lenticule extraction, a laser in situ keratomileusis-like flap allowed removal of the lenticule, whereas in small-incision lenticule extraction, it was removed through a small incision. Follow-up was 6 months. RESULTS: Thirty-five patients were treated with femtosecond lenticule extraction in 1 eye and small-incision lenticule extraction in the other. The mean preoperative spherical equivalent was -7.6 diopters (D) ± 1.0 (SD) (range -6.0 to -9.9 D). After both procedures, 90% of eyes had an uncorrected distance visual acuity of 20/40 or better 1 day postoperatively, increasing to 100% after 6 months. At 6 months, the mean corrected distance visual acuity (CDVA) improved significantly by approximately 1.5 letters on the logMAR chart. No eyes lost or gained 2 lines or more of CDVA after either procedure. The achieved refraction was a mean of -0.04 ± 0.38 D from the attempted refraction after femtosecond lenticule extraction and -0.09 ± 0.39 D after small-incision lenticule extraction. After both procedures, 88% of eyes were within ±0.50 D. Contrast sensitivity was unchanged. The changes in higher-order aberrations were similar. CONCLUSION: The all-femtosecond laser flap-based and cap-based techniques produced almost identical results up to 6 months postoperatively in eyes with moderate to high myopia.

Subbasal nerve morphology, corneal sensation, and tear film evaluation after refractive femtosecond laser lenticule extraction.

BACKGROUND: The purpose of this study was to compare corneal subbasal nerve morphology, corneal sensation, and tear film parameters after femtosecond lenticule extraction (FLEX) and small-incision lenticule extraction (SMILE). METHODS: A prospective, randomized, single-masked, paired-eye design clinical trial of 35 patients treated for moderate to high myopia with FLEX in one eye and SMILE in the other. In both techniques, an intrastromal lenticule was cut by a femtosecond laser and manually extracted. In FLEX, a LASIK-like flap allowed removal of the lenticule, whereas in SMILE, it was removed through a small incision. In-vivo confocal microscopy was used to acquire images of the central corneal subbasal nerve plexus, from which nerve density, total nerve number, and nerve tortuosity were analyzed. Corneal sensation was measured using Cochet-Bonnet esthesiometry. A visual analog scale, tear osmolarity, non-invasive tear film break-up time (keratograph) tear meniscus height (anterior segment OCT), Schirmer's test, and fluorescein tear film break-up time were used to evaluate tear film and ocular surface symptoms. Patients were examined before and 6 months after surgery. RESULTS: There were no statistically significant differences in baseline parameters between FLEX and SMILE (p > 0.050). With regard to changes from before to 6 months after surgery, mean reduction in subbasal nerve density was 14.22 ± 6.24 mm/mm(2) in FLEX eyes, and 9.21 ± 7.80 mm/mm(2) in SMILE eyes (p < 0.05). The total number of nerves decreased more in FLEX eyes than in SMILE eyes (p < 0.05). No change was found when comparing tortuosity (p > 0.05). Corneal sensation was reduced with 0.38 ± 0.49 cm in FLEX eyes, and 0.10 ± 0.34 cm in SMILE eyes (p < 0.01). No differences were found between FLEX and SMILE in tear film evaluation tests (p > 0.05). Significantly more patients felt postoperative foreign body sensation in the FLEX eye within the first days after surgery, as compared to the SMILE eye. CONCLUSIONS: Six months after surgery, the less invasive SMILE technique seemed better at sparing the central corneal nerves as compared to FLEX. Corneal sensation was only significantly reduced in FLEX eyes. There were no differences between FLEX and SMILE when comparing tear film evaluation tests 6 months after surgery.

Long-term outcomes of photorefractive keratectomy for low to high myopia: 13 to 19 years of follow-up.

PURPOSE: To evaluate long-term outcomes after photorefractive keratectomy (PRK). METHODS: A retrospective follow-up study of patients who received PRK at 5.0- to 6.5-mm optical zones, using the Summit broad beam excimer laser (Summit Technology, Inc., Waltham, MA) at Odense University Hospital, Odense, Denmark, between 1992 and 1998. One randomly selected eye of each patient was used in the statistical analyses. Re-treated eyes were excluded. RESULTS: One hundred sixty eyes were included. Mean follow-up time was 16 years (range: 13 to 19 years). Mean preoperative spherical equivalent was -4.84 ± 2.95 diopters (D) (range: -20.25 to -1.25 D). At last follow-up examination, achieved refraction was -1.00 ± 1.56 D (range: -10.75 to +1.00 D) from attempted refraction, and the change in mean refractive error from 6 months postoperatively was less than 1.00 D. Results from a subgroup of unilateral treated patients indicated that myopic progression was the main reason for the residual refractive error. For eyes with low myopia (n = 124), the proportion of eyes within ± 1.0 D of attempted refraction was 72%, and for eyes with high myopia (-6.00 D or more, n = 36) it was 47%. Forty-five percent had uncorrected distance visual acuity of 20/20 or better at last follow-up examination. Three eyes (2%) lost two or more lines and 13 eyes (8%) gained two or more lines of corrected distance visual acuity. Fourteen percent had haze (grade 0.5 to 2). Eighty-one percent were satisfied with the surgery. CONCLUSION: PRK for low degrees of myopia seemed safe and effective up to 19 years after surgery with conventional broad beam laser ablation. Refractive predictability was significantly lower and the occurrence of haze was higher in eyes with high myopia.

Predictors for the outcome of small-incision lenticule extraction for Myopia.

PURPOSE: To study the influence of patient- and surgery-related parameters on the predictability, efficacy, and safety of small-incision lenticule extraction (SMILE) for treatment of myopia. METHODS: This prospective, clinical quality, control study comprised 670 eyes from 335 patients with myopia up to -10.00 diopters (D) (spherical equivalent refraction) and astigmatism up to 2.00 D treated with SMILE in both eyes and followed for 3 months. RESULTS: Preoperative mean spherical equivalent refraction was -7.19±1.30 D. In eyes with emmetropia as the target refraction, 84% obtained uncorrected distance visual acuity ≤ 0.10 logMAR (20/25 or better Snellen equivalent) at 3 months. Mean corrected distance visual acuity (CDVA) improved from -0.03 to -0.05 logMAR (P<.01). Two or more lines of CDVA were lost in 2.4% (16 eyes). The achieved refraction was 0.25±0.44 D less than attempted after 3 months, and 80% (537 eyes) and 94% (631 eyes) were within ±0.50 and ±1.00 D of attempted correction, respectively. Multiple linear regression analyses revealed that spherical equivalent refraction undercorrection was predicted by increasing patient age (0.10 D per decade; P<.01) and steeper corneal curvature (0.04 D per D; P<.01). Safety and efficacy of the procedure were minimally affected by age, gender, and simultaneous cylinder correction. CONCLUSIONS: Undercorrection of 0.25 D and small effects of patient age and corneal curvature suggest that the standard nomogram for SMILE need only minor adjustments. This study suggests that safety and efficacy are not influenced to any clinically significant degree by easily discernible patient factors.