Corneal stromal localization of TGF beta isoforms in spontaneous persistent epithelial defects after PRK in rabbits.

The purpose of this study was to evaluate transforming growth factor beta (TGFß) isoform localization in rabbit corneas with spontaneous persistent epithelial defects (PEDs) after photorefractive keratectomy (PRK). Four cryofixed corneas from a previously reported series of PEDs in rabbits that had PRK were evaluated with triplex immunohistochemistry (IHC) for TGFß3, myofibroblast marker alpha-smooth muscle actin (α-SMA) and mesenchymal marker vimentin. One cornea had sufficient remaining tissue for triplex IHC for TGFß1, TGFß2, or TGFß3 (each with α-SMA and vimentin) using isoform-specific antibodies. All three TGFß isoforms were detected in the subepithelial stroma at and surrounding the PED. Some of each TGFß isoform co-localized with α-SMA of myofibroblasts, which could be TGFß isoform autocrine production by myofibroblasts or TGFß-1, -2, and -3 binding to these myofibroblasts.

Topical Losartan Inhibition of Myofibroblast Generation in Rabbit Corneas With Acute Incisions.

PURPOSE: The purpose of this study was to study whether deep central corneal incisions close during topical losartan treatment and the effect of topical losartan on myofibroblast generation after incisions in rabbit corneas. METHODS: Rabbits (12) had a 0.35-mm deep radial incision from the center of the cornea into the limbus in 1 eye that was approximated with a single 10-0 nylon suture 1 mm inside the limbus. The incision was treated with 50 µL of topical 0.8 mg/mL losartan or 50 µL of balanced salt solution vehicle 6 times per day for 1 month. Standardized slitlamp photographs of the central incisions were analyzed for opacity with ImageJ before euthanasia. Triplex IHC was performed on cryofixed corneas for myofibroblast marker alpha-smooth muscle actin, mesenchymal cell marker vimentin, and basement membrane marker laminin alpha-5. Stromal α-SMA-positive myofibroblasts surrounding the incisions were quantitated with ImageJ. RESULTS: Topical losartan compared with vehicle did not affect closure of the radial incisions or the opacity that developed surrounding the incisions at 1 month after injury. Topical losartan compared with vehicle did significantly decrease the average density of stromal myofibroblasts surrounding the incisions. CONCLUSIONS: Topical losartan, a known inhibitor of transforming growth factor beta signaling, did not affect closure of deep corneal incisions. Losartan decreased myofibroblast generation surrounding nearly full-thickness radial corneal incisions compared with vehicle. The opacity at the incisions was not significantly affected by losartan-likely because corneal fibroblasts that develop in the stroma adjacent to the incisions were not changed by the losartan compared with the vehicle.

Toric Monofocal Intraocular Lenses for the Correction of Astigmatism during Cataract Surgery: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the published literature evaluating the visual and refractive outcomes and rotational stability of eyes implanted with toric monofocal intraocular lenses (IOLs) for the correction of keratometric astigmatism during cataract surgery and to compare those outcomes with outcomes of eyes implanted with nontoric monofocal IOLs and other astigmatism management methods performed during cataract surgery. This assessment was restricted to the toric IOLs available in the United States. METHODS: A literature search of English-language publications in the PubMed database was last conducted in July 2022. The search identified 906 potentially relevant citations, and after review of the abstracts, 63 were selected for full-text review. Twenty-one studies ultimately were determined to be relevant to the assessment criteria and were selected for inclusion. The panel methodologist assigned each a level of evidence rating; 12 studies were rated level I and 9 studies were rated level II. RESULTS: Eyes implanted with toric IOLs showed excellent postoperative uncorrected distance visual acuity (UCDVA), reduction of postoperative refractive astigmatism, and good rotational stability. Uncorrected distance visual acuity was better and postoperative cylinder was lower with toric IOLs, regardless of manufacturer, when compared with nontoric monofocal IOLs. Correcting pre-existing astigmatism with toric IOLs was more effective and predictable than using corneal relaxing incisions (CRIs), especially in the presence of higher magnitudes of astigmatism. CONCLUSIONS: Toric monofocal IOLs are effective in neutralizing pre-existing corneal astigmatism at the time of cataract surgery and result in better UCDVA and significant reductions in postoperative refractive astigmatism compared with nontoric monofocal IOLs. Toric IOLs result in better astigmatic correction than CRIs, particularly at high magnitudes of astigmatism. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Late approach for LASIK flap striae.

A 24-year-old man was referred for postrefractive surgery evaluation. The patient had a history of uneventful laser in situ keratomileusis (LASIK) in both eyes 3 months previously. According to the surgeon who originally performed the surgery, on slitlamp examination, only microstriae in the left eye was detected on postoperative day 1 and a more conservative follow-up approach was adopted without further immediate intervention. The patient returned only 3 months after surgery, complaining of low vision in the left eye that, according to the patient, had been present since postoperative week 2. The patient was then referred for examination and surgical procedure with a diagnosis of significant postoperative striae. The slitlamp examination revealed a LASIK flap with striae, epithelial filling, and a wrinkled appearance (Figure 1JOURNAL/jcrs/04.03/02158034-202312000-00017/figure1/v/2023-11-20T151558Z/r/image-tiff). There were no signs of infection or inflammation. Originally, the LASIK flap was programmed to be 110 µm. Preoperative manifest refraction in the right eye was -5.25 (20/20) and in the left eye was -5.25 (20/20). Assuming it is a case of late-approach LASIK flap striae, how would you proceed? Would you try to hydrate and lift the flap and just reposition it? Would you avoid lifting and associate phototherapeutic keratectomy (PTK) with excimer laser on top of the flap? Would you consider topo-guided surgery with regularization of the visual axis or even amputation of the flap?

Topical Losartan Decreases Myofibroblast Generation But Not Corneal Opacity After Surface Blast-Simulating Irregular PTK in Rabbits.

Purpose: To evaluate the efficacy of topical losartan after blast injury-simulating irregular phototherapeutic keratectomy (PTK) in rabbits. Methods: Twelve NZW rabbits underwent 100 pulse 6.5 mm diameter PTK over a metal screen to generate severe surface irregularity and inhibit epithelial basement membrane regeneration. Corneas were treated with 0.8 mg/mL losartan in balanced salt solution (BSS) or BSS 50 µL six times per day for six weeks after PTK. All corneas had slit lamp photography, with and without 1% fluorescein at two, four, and six weeks after PTK, and were analyzed using immunohistochemistry for the myofibroblast marker α-smooth muscle actin (α-SMA), keratocyte marker keratocan, mesenchymal cell marker vimentin, transforming growth factor (TGF)-ß1, and collagen type IV. Results: Topical 0.8 mg/mL losartan six times a day significantly decreased anterior stromal α-SMA intensity units compared to BSS at six weeks after anterior stromal irregularity-inducing screened PTK (P = 0.009). Central corneal opacity, however, was not significantly different between the two groups. Keratocan, vimentin, TGF-ß1, or collagen type IV levels in the anterior stroma were not significantly different between the two groups. Conclusions: Topical losartan effectively decreased myofibroblast generation after surface blast simulation irregular PTK. However, these results suggest initial masking-smoothing PTK, along with adjuvant topical losartan therapy, may be needed to decrease corneal stromal opacity after traumatic injuries that produce severe surface irregularity. Translational Relevance: Topical losartan decreased scar-producing stromal myofibroblasts after irregular PTK over a metal screen but early smoothing of irregularity would also likely be needed to significantly decrease corneal opacity.

Cell Biology of Spontaneous Persistent Epithelial Defects After Photorefractive Keratectomy in Rabbits.

Purpose: To evaluate wound healing in rabbit corneas that developed a spontaneous persistent epithelial defect (PED) after photorefractive keratectomy (PRK). Methods: Forty-eight 10- to 15-week-old female New Zealand White rabbits weighing 2.5 to 3.0 kg underwent either -3 diopter (D) or -9 D PRK to generate a series of corneas to study wound healing after injury. During that series, seven corneas developed a PED detected with 1% fluorescein staining at a slit lamp that either did not have epithelial closure by 1 week after surgery or subsequently had the closed epithelium break down to form a PED 2 to 3 weeks after surgery. The corneas had slit-lamp photography, with and without 1% fluorescein, and were removed from the normal PRK series. Each PED cornea was evaluated using immunohistochemistry for the myofibroblast marker α-smooth muscle actin (α-SMA), keratocyte marker keratocan, and mesenchymal cell marker vimentin, as well as basement membrane components perlecan and collagen type IV. Results: All seven corneas that had PRK with a PED, even the two evaluated at only 1 week after PRK, had α-SMA-positive myofibroblasts populating the anterior stroma within the PED, along with comingled α-SMA-negative cells that were likely corneal fibroblasts and possibly bone marrow-derived fibrocytes. Both perlecan and collagen type IV accumulated in the anterior stroma of the epithelial defects without an epithelial basement membrane, likely produced by corneal fibroblasts to modulate transforming growth factor-ß entering the stroma from the tears and peripheral epithelium. Conclusions: Corneas with a PED that occurred following PRK (a procedure that produces a transient neurotropic state in the cornea) had myofibroblasts populating the superficial stroma within the epithelial defect as early as 1 week after the surgery. Translational Relevance: Pharmacologic treatments that trigger myofibroblast apoptosis, including topical losartan, could facilitate decreased scarring fibrosis in corneas with a PED.

Therapeutic visual rehabilitation in a patient with high hyperopia and flat cornea years after radial keratotomy.

A 51-year-old man was referred for refractive surgery evaluation. Spectacle dependence and poor visual quality in both eyes was his chief complaint. He cannot tolerate contact lenses. Corrected distance visual acuity (CDVA) was 20/40 in both eyes. Manifest refraction was +5.25 -2.25 @ 90 (20/40) in the right eye and +6.25 -2.25 @ 105 (20/40) in the left eye. The patient had a history of radial keratotomy (RK) almost 30 years ago in both eyes and at the slitlamp presented 8 RK incisions, proportionally spaced between one another. All incisions were closed, and there were no relevant signs of scarring. The patient denied any history of ocular trauma, systemic disease, or medications. Corneal topography with different technologies revealed an irregular pattern with marked central flattening in both eyes, with some points below 30 diopters (D) (Supplemental Figures 1 and 2, available at http://links.lww.com/JRS/A862 and http://links.lww.com/JRS/A863, respectively). There were no signs of cataract, and fundus examination was normal. Optical coherence tomography (OCT) of the right eye revealed a more homogeneous thickness pattern, little variation between the thinnest and thickest areas, and adequate transparency (Figure 1JOURNAL/jcrs/04.03/02158034-202306000-00018/figure1/v/2023-05-31T172126Z/r/image-tiff). In the left eye, there is wide variability between the thinnest and thickest stromal points, with annular thinning and central thickening (Figure 2JOURNAL/jcrs/04.03/02158034-202306000-00018/figure2/v/2023-05-31T172126Z/r/image-tiff). Both eyes show marked epithelial irregularity. Considering this patient's current ocular status, how would you reach visual rehabilitation? Because he is contact lens intolerant, would you consider surface ablation, for example, photorefractive keratectomy (PRK) with mitomycin-C (MMC)? If that were the case, would you think of an optimized or a topography-guided (TG) treatment? Would you immediately consider a corneal transplant option? Would you instead consider a more conservative approach? Which one and why?

Management of Pain after Photorefractive Keratectomy: A Report by the American Academy of Ophthalmology.

OBJECTIVE: To evaluate current best practices for postoperative photorefractive keratectomy (PRK) pain control. METHODS: Literature searches in the PubMed database were last conducted in October 2021 and were restricted to publications in English. This search identified 219 citations, of which 84 were reviewed in full text for their relevance to the scope of this assessment. Fifty-one articles met the criteria for inclusion; 16 studies were rated level I, 33 studies were rated level II, and 2 studies were rated level III. RESULTS: Systemic opioid and nonsteroidal anti-inflammatory drugs (NSAIDs); topical NSAIDs; postoperative cold patches; bandage soft contact lenses (BCLs), notably senofilcon A contact lenses; and topical anesthetics were demonstrated to offer significantly better pain control than comparison treatments. Some other commonly reported pain mitigation interventions such as systemic gabapentinoids, chilled intraoperative balanced salt solution (BSS) irrigation, cycloplegia, and specific surface ablation technique strategies offered limited improvement in pain control over control treatments. CONCLUSIONS: Systemic NSAIDs and opioid medications, topical NSAIDs, cold patches, BCLs, and topical anesthetics have been shown to provide improved pain control over alternative strategies and allow PRK-associated pain to be more tolerable for patients.

Role of Corneal Epithelial Measurements in Differentiating Eyes with Stable Keratoconus from Eyes that Are Progressing.

Purpose: To evaluate measures of corneal epithelium in eyes that showed documented signs of keratoconus (KC) progression and compare with stable eyes and healthy controls. Also, to determine the correlation of these epithelial parameters with maximum keratometry (K max) and pachymetry. Design: Prospective, observational, comparative study. Participants: One-hundred and fifty eyes from 150 patients. The study included 50 eyes from patients with documented KC progression, 50 eyes with stable KC, and 50 clinically normal eyes to serve as controls. Methods: A spectral-domain (SD)-OCT imaging was obtained in all eyes, and mean values were compared between the groups. The correlation of epithelial parameters with K max and thinnest pachymetry was also investigated. Main Outcome Measures: For the purposes of this study, the epithelial measures maximum, minimum, superior, and inferior values as well as the difference between the minimum and maximum (min-max) and epithelial standard deviation were considered, obtained from SD-OCT and compared between groups. Measurements of the thinnest point and min-max in pachymetry were also recorded. Results: The only epithelial parameter that presented a statistically significant difference between stable and progressive KC was epithelium min-max. Although stable KC presented epithelium min-max mean values of -18.2 ± 6.6, progressive KC eyes presented mean values of -23.4 ± 10.3 (P < 0.0001). Epithelial maximum (P = 0.16), minimum (P = 0.25), superior (P = 0.28), inferior (P = 0.23), and standard deviation (P = 0.25) values were not significantly different between stable and progressive eyes. Difference min-max pachymetry points in stable (-108.3 ± 33.5) and progressive KC (-115.2 ± 56.0) were not significantly different (P = 0.723). There was no significant correlation between epithelium min-max with corneal thinning (P = 0.39) or K max (P = 0.09) regardless of disease progression. Conclusions: Epithelial measures are useful to identify KC eyes that are progressing; the parameters that measure the difference between min-max epithelium points were significantly different between stable and progressive groups, unlike this difference in pachymetry. Finally, this epithelial parameter seems to be independent of corneal thinning and K max. Financial Disclosures: Proprietary or commercial disclosure may be found after the references.

Agreement between corneal diameter measurements obtained with an optical biometer and a Placido-based topographer / Acordo de medições do diâmetro da córnea obtidas por um biômetro óptico e um topógrafo com base em Plácido

ABSTRACT Purpose: The purpose of this study was to compare the white-to-white distance measurements of two devices (IOL Master 500 and Atlas corneal topographer) commonly used in clinical practice to determine if they were interchangeable. Providing information on instrument interchangeability could eliminate several unnecessary tests and consequently reduce the economic burden for the patient and society. Methods: In this prospective, comparative case series, the white-to-white distance was measured by independent examiners using the Atlas topographer (Carl Zeiss Meditec) and the IOL Master 500 (Carl Zeiss Meditec). One eye each of 184 patients was tested. Statistical analyses were performed using a paired t-test, Pearson correlation analysis, and Bland-Altman analysis to compare the measurement methods. Results: The mean white-to-white distance measurements with the Atlas topographer and the IOL Master 500 were 12.20 ± 0.44 mm and 12.12 ± 0.41 mm, respectively (p<0.001). The mean white-to-white difference between the two devices was 0.07 mm (95% confidence interval of mean difference: 0.04-0.11 mm). The Pearson correlation coefficient between the two devices was 0.85 (p<0.0001). The 95% limits of agreement between the two devices were -0.38 mm to 0.53 mm. Conclusions: The Atlas topographer and IOL Master 500 can be used interchangeably with respect to white-to-white distance measurements, as the range of differences is unlikely to affect clinical practice and decision making.

RESUMO Objetivo: O objetivo deste estudo é comparar as medições de diâmetro corneano de dois dispositivos normalmente utilizados na prática clínica (IOL Master 500 e Atlas topógrafo corneal) para ver se são permutáveis. O fornecimento de informações sobre a permutabilidade de instrumentos poderia eliminar vários testes desnecessários e, consequentemente, reduzir a carga econômica para o paciente e para a sociedade. Métodos: Nesta série de casos prospectivos e comparativos, a distância do diâmetro corneano foi medida por examinadores independentes utilizando o Topógrafo Atlas (Carl Zeiss Meditec) e o IOL Master 500 (Carl Zeiss Meditec), em um olho de 184 pacientes. A análise estatística foi realizada utilizando o teste t pareado, a correlação Pearson e a análise Bland-Altman para comparar os métodos de medição. Resultados: As medições médias da distância do diâmetro corneano com o topógrafo Atlas e o IOL Master 500 foram de 12,20 ± 0,44 mm e 12,12 ± 0,41 mm, respectivamente (p<0,001). A diferença média de WTW entre os dois dispositivos foi de 0,07 mm (intervalo de confiança de 95% da diferença média: 0,04 - 0,11 mm). O coeficiente de correlação Pearson entre os dois dispositivos foi de 0,85, p<0,0001. Os limites de concordância de 95% entre os dois dispositivos foram de -0,38 mm a 0,53 mm. Conclusões: O Atlas topographer e o IOL Master 500 podem ser utilizados permutavelmente em relação à medição do diâmetro corneano, uma vez que a gama de diferenças encontradas é pouco susceptível de afetar a prática clínica e a tomada de decisões.

Losartan Inhibition of Myofibroblast Generation and Late Haze (Scarring Fibrosis) After PRK in Rabbits.

PURPOSE: To study the effect of topical losartan compared to vehicle on the generation of myofibroblasts and development of late haze scarring fibrosis after photorefractive keratectomy (PRK) in rabbits. METHODS: Twelve rabbits had -9.00 diopter (D) PRK in one eye followed by 50 µL of topical 0.2 mg/mL losartan or 50 µL of vehicle six times per day for 1 month. Standardized slit-lamp photographs were obtained prior to death. Duplex immunohistochemistry was performed on cryofixed corneas for myofibroblast marker alpha-smooth muscle actin (α-SMA) and keratocyte marker keratocan or collagen type IV and transforming growth factor (TGF)-ß1. ImageJ software (National Institutes of Health) was used for quantitation. RESULTS: Topical losartan compared to vehicle significantly decreased corneal opacity (P = .04) and anterior stromal myofibroblast generation (P = .01) at 1 month after PRK. Topical losartan compared to vehicle also decreased anterior stromal non-basement membrane collagen type IV at 1 month after PRK (P = .004). CONCLUSIONS: Topical angiotensin converting enzyme II receptor inhibitor losartan, a known inhibitor of TGF-ß signaling, decreased late haze scarring fibrosis and myofibroblast generation after -9.00 D PRK in rabbits compared to vehicle. It also decreases TGF-ß-modulated, corneal fibroblast-produced, non-basement membrane stromal collagen type IV-likely also through inhibition of TGF-ß signaling. [J Refract Surg. 2022;38(12):820-829.].

Early LASIK flap displacement without signs of infection.

A 37-year-old woman was referred for refractive surgery evaluation. Poor visual quality in her left eye is her chief concern. The patient had undergone laser in situ keratomileusis (LASIK) in both eyes 3 days previously. Detailed history revealed that the patient underwent surgery to correct low myopia and astigmatism (-2.50 -2.75 × 180 in the right eye and -1.25 -2.75 × 180 in the left eye). The preoperative evaluation corrected distance visual acuity (CDVA) was 20/20 in the right eye and 20/20 in the left eye. The surgery was performed with a mechanical microkeratome and was uneventful. The patient reports that after her vision improved on the first day, she woke up with blurry vision in her left eye on the second day and it remained that way until the third day when she sought medical help. The slitlamp examination showed LASIK flap displacement without signs of infection ( Figure 1JOURNAL/jcrs/04.03/02158034-202212000-00023/figure1/v/2022-12-01T092452Z/r/image-tiff ). The patient was using topical corticosteroids and topical antibiotics every 6 hours. Considering the likely stromal exposure time, what would be the best approach for this case? Does the probable time of displacement of this flap change its behavior? In what way? If you decide to reposition the flap, would it be interesting to use fibrin glue or suture? Considering that there was no major trauma in the patient's report, what is the importance of the LASIK flap having been created by a mechanical microkeratome and not by a femtosecond laser in the displacement of the flap?

Ectasia Risk Model: A Novel Method Without Cut-off Point Based on Artificial Intelligence Improves Detection of Higher-Risk Eyes.

PURPOSE: To develop a new ectasia risk model through artificial intelligence (AI) and machine learning, enabling the creation of an integrated method without a cut-off point per risk factor, and subsequently better at differentiating patients at higher risk of ectasia with normal topography. METHODS: This comparative case-control study included 339 eyes with normal preoperative topography, with 65 eyes that developed ectasia after laser in situ keratomileusis (ectasia group) and 274 eyes that did not develop ectasia (control group). The AI model used known risk factors to engineer 14 additional ones, totaling 20 features. In this methodology, no variable is used in isolation because its cut-off point is never considered. All separation between cases and controls is made through the interaction detected by the machine learning model that gathers the variables considered relevant. The ability to correctly separate ectatic cases identified as high risk, ectatic cases wrongly classified as low risk, and controls were illustrated by the diagram t-distributed stochastic neighbor embedding (t-SNE). RESULTS: Only two original variables (percent tissue altered and corneal thickness) and two derived from the feature engineering process (derivative percent tissue altered and age weighted value) were selected by the final AI model (ie, best performing AI-based model to separate patients at higher risk). The t-SNE visualization demonstrated the greater ability to differentiate between patients considered at risk by the AI-based model, without a cut-off point, compared to all other methods used alone (P < .0001). CONCLUSIONS: This study describes a new AI-based model that integrates different risk factors without a cut-off point, increasing the number of cases correctly identified as at higher risk. [J Refract Surg. 2022;38(11):716-724.].

Agreement between corneal diameter measurements obtained with an optical biometer and a Placido-based topographer.

PURPOSE: The purpose of this study was to compare the white-to-white distance measurements of two devices (IOL Master 500 and Atlas corneal topographer) commonly used in clinical practice to determine if they were interchangeable. Providing information on instrument interchangeability could eliminate several unnecessary tests and consequently reduce the economic burden for the patient and society. METHODS: In this prospective, comparative case series, the white-to-white distance was measured by independent examiners using the Atlas topographer (Carl Zeiss Meditec) and the IOL Master 500 (Carl Zeiss Meditec). One eye each of 184 patients was tested. Statistical analyses were performed using a paired t-test, Pearson correlation analysis, and Bland-Altman analysis to compare the measurement methods. RESULTS: The mean white-to-white distance measurements with the Atlas topographer and the IOL Master 500 were 12.20 ± 0.44 mm and 12.12 ± 0.41 mm, respectively (p<0.001). The mean white-to-white difference between the two devices was 0.07 mm (95% confidence interval of mean difference: 0.04-0.11 mm). The Pearson correlation coefficient between the two devices was 0.85 (p<0.0001). The 95% limits of agreement between the two devices were -0.38 mm to 0.53 mm. CONCLUSIONS: The Atlas topographer and IOL Master 500 can be used interchangeably with respect to white-to-white distance measurements, as the range of differences is unlikely to affect clinical practice and decision making.

Accuracy of the Preoperative Predicted Percentage of Tissue Altered Calculation in Refractive Surgery Planning for Myopic LASIK.

PURPOSE: To determine the reliability of the percentage of tissue altered (PTA) calculation as part of the planning strategy for myopic laser in situ keratomileusis (LASIK) by comparing the estimated PTA provided by preoperative calculation to the postoperative PTA actually achieved in microkeratome-assisted myopic LASIK. METHODS: This retrospective study included 3,624 eyes of 3,624 patients who underwent mechanical microkeratome-assisted LASIK surgery for myopic correction. The calculated preoperative PTA values based on the planned flap thickness and ablation depth were compared with the actual achieved postoperative PTA using the difference of corneal central thickness postoperatively for assessing the achieved ablation depth and the intraoperative ultrasound-assisted flap thickness measurement. Regression analysis was performed to reveal preoperative parameters that might influence PTA calculation accuracy. RESULTS: The mean difference between the estimated and achieved PTA was 0.451 ± 3.45% (P < .001) (95% CI: 0.3708 to 0.5322) with a preoperative and postoperative mean PTA of 31.07 ± 4.07% and 31.52 ± 5.78%, respectively. The differences between the achieved and planned maximum ablation depth and flap thickness were 4.32 ± 13.70 µm (P < .001) and -1.61 ± 13.66 µm (P < .001), respectively. CONCLUSIONS: Although a statistically significant difference was found between the preoperative calculated PTA and actually achieved PTA, the difference in PTA value (less than 1%) was clinically non-significant and indicated a highly reliable metric for preoperative refractive surgery planning. [J Refract Surg. 2022;38(7):422-427.].

Topical Losartan and Corticosteroid Additively Inhibit Corneal Stromal Myofibroblast Generation and Scarring Fibrosis After Alkali Burn Injury.

Purpose: To evaluate the efficacy of losartan and prednisolone acetate in inhibiting corneal scarring fibrosis after alkali burn injury in rabbits. Methods: Sixteen New Zealand White rabbits were included. Alkali injuries were produced using 1N sodium hydroxide on a 5-mm diameter Whatman #1 filter paper for 1 minute. Four corneas in each group were treated six times per day for 1 month with 50 µL of (1) 0.8 mg/mL losartan in balanced salt solution (BSS), (2) 1% prednisolone acetate, (3) combined 0.8 mg/mL losartan and 1% prednisolone acetate, or (4) BSS. Area of opacity and total opacity were analyzed in standardized slit-lamp photos with ImageJ. Corneas in both groups were cryofixed in Optimal cutting temperature (OCT) compound at 1 month after surgery, and immunohistochemistry was performed for alpha-smooth muscle actin (α-SMA) and keratocan or transforming growth factor ß1 and collagen type IV with ImageJ quantitation. Results: Combined topical losartan and prednisolone acetate significantly decreased slit-lamp opacity area and intensity, as well as decreased stromal myofibroblast α-SMA area and intensity of staining per section and confined myofibroblasts to only the posterior stroma with repopulation of the anterior and mid-stroma with keratocan-positive keratocytes after 1 month of treatment. Corneal fibroblasts produced collagen type IV not associated with basement membranes, and this production was decreased by topical losartan. Conclusions: Combined topical losartan and prednisolone acetate decreased myofibroblast-associated fibrosis after corneal alkali burns that produced full-thickness injury, including corneal endothelial damage. Increased dosages and duration of treatment may further decrease scarring fibrosis. Translational Relevance: Topical losartan and prednisolone acetate decrease myofibroblast-mediated scarring fibrosis after corneal injury.

Femtosecond Laser-Assisted Cataract Surgery: A Report by the American Academy of Ophthalmology.

PURPOSE: To evaluate refractive outcomes, safety, and cost-effectiveness of femtosecond laser-assisted cataract surgery (FLACS) compared with phacoemulsification cataract surgery (PCS). METHODS: A PubMed search of FLACS was conducted in August 2020. A total of 727 abstracts were reviewed and 33 were selected for full-text review. Twelve articles met inclusion criteria and were included in this assessment. The panel methodologist assigned a level of evidence rating of I to all 12 studies. RESULTS: No significant differences were found in mean uncorrected distance visual acuity, best-corrected distance visual acuity, or the percentage of eyes within ± 0.5 and ± 1 diopter of intended refractive target between FLACS and PCS. Intraoperative and postoperative complication rates were similar between the 2 groups, and most studies showed no difference in endothelial cell loss between FLACS and PCS at various time points between 1 and 6 months. In large randomized controlled studies in the United Kingdom and France, FLACS was less cost-effective than PCS. CONCLUSIONS: Both FLACS and PCS have similar excellent safety and refractive outcomes. At this time, one technique is not superior to the other, but economic analyses performed in some populations have shown that FLACS is less cost-effective.

Epithelial Basement Membrane Regeneration After PRK-Induced Epithelial-Stromal Injury in Rabbits: Fibrotic Versus Non-fibrotic Corneal Healing.

PURPOSE: To study epithelial basement membrane (EBM) regeneration in non-fibrotic and fibrotic corneas after photorefractive keratectomy (PRK). METHODS: Rabbits (120 total) had either epithelial scrape alone, -4.50 diopters (D) PRK, -9.00 D PRK, or no surgery. Immunohistochemistry was performed on cryofixed corneas at time points from unwounded to 8 weeks (four corneas at each time point in each group). Multiplex immunohistochemistry was performed for EBM components, including collagen type IV, laminin beta-3, laminin alpha-5, perlecan, and nidogen-1. Stromal cellular composition was studied by triplex immunohistochemistry for keratocan, vimentin, and alpha-smooth muscle actin (SMA). RESULTS: PRK-injured EBM significantly regenerated by 4 days after surgery. However, early TGF-beta-regulating perlecan incorporation into the nascent EBM declined 4 to 7 days after surgery in fibrotic corneas. Non-fibrotic corneas that had fully regenerated EBM (with all five components incorporated into the EBM) were transparent and had few SMA-positive myofibroblasts in the stroma. Conversely, corneas with defective nascent EBM that lacked perlecan developed many anterior stromal myofibroblasts and fibrosis at 3 to 4 weeks after surgery and had large amounts of collagen type IV in the nascent EBM and anterior stroma. Myofibroblasts synthesized perlecan but were incompetent to incorporate the heparin sulfate proteoglycan into the nascent EBM. Corneal transparency was restored over several months even in fibrotic corneas, and this was associated with a return of EBM perlecan, myofibroblast disappearance, and reabsorption of disordered extracellular matrix. CONCLUSIONS: Defective incorporation of perlecan into the regenerating EBM by subepithelial myofibroblasts, and likely their precursor cells, underlies the development and persistence of stromal fibrosis after PRK corneal injury. [J Refract Surg. 2022;38(1):50-60.].

Topical losartan inhibits corneal scarring fibrosis and collagen type IV deposition after Descemet's membrane-endothelial excision in rabbits.

The purpose of this study was to examine the effect of topical and/or oral angiotensin converting enzyme II inhibitor and TGF-beta signaling blocker losartan on corneal stromal fibrosis that developed in rabbit corneas after Descemetorhexis removal of central Descemet's membrane and corneal endothelium. Twenty-eight New Zealand white rabbits were included and either had 8 mm central Descemetorhexis or sham control surgery without Descemetorhexis in one eye. Groups of 4 eyes without Descemetorhexis were treated for one month with no medications, topical losartan or oral losartan. Groups of 4 eyes with Descemetorhexis were treated with topical and oral vehicle, topical losartan, oral losartan, or both topical losartan and oral losartan for one month. Standardized slit lamp photos were obtained with central opacity intensity measured with ImageJ. The posterior fibrotic zone of corneas was measured on immunohistochemistry for alpha-smooth muscle actin (SMA) and keratocan using QuPath analysis. Collagen type IV expression in the posterior cornea was quantitated with ImageJ and duplex immunohistochemistry for collagen type IV and TGF beta-1. After Descemetorhexis, topical, but not oral, losartan decreased the intensity of central stromal opacity, reduced peripheral corneal scarring, and decreased alpha-smooth muscle actin myofibroblast fibrosis area compared to corneas that had Descemetorhexis and treatment with vehicles alone. Topical losartan decreased posterior stromal cellular, non-Descemet's membrane, collagen type IV production, that is likely stimulated by TGF beta as part of a negative regulatory feedback mechanism, compared to vehicle treatment at one month after Descemetorhexis. Topical losartan is likely to be effective in reducing corneal scarring fibrosis produced by traumatic injury, microbial infection, and some corneal diseases and surgeries.

Intrastromal corneal ring segments followed by PRK for postkeratoplasty high astigmatism: prospective study.

PURPOSE: To evaluate refractive and topographic results of the association of intrastromal corneal ring segments (ICRS) with photorefractive keratectomy (PRK) for the correction of high (>6.0 diopters [D]) postkeratoplasty astigmatism (PKA). SETTING: University of São Paulo, São Paulo, Brazil. DESIGN: Prospective interventional study. METHODS: Postpenetrating keratoplasty patients, intolerant to contact lens fitting, and with corneal astigmatism higher than 6.0 D were treated by the combination of ICRS and PRK from January 2017 to June 2019. First, patients underwent femtosecond laser-assisted ICRS implantation to reduce and regularize corneal astigmatism, and 3 months later, submitted to PRK for the residual astigmatism. Outcomes were obtained 12 months after PRK. RESULTS: The study comprised 30 eyes of 29 patients. Mean uncorrected distance visual acuity (logMAR) changed from 1.16 ± 0.37 in the preoperative to 0.69 ± 0.40 after ICRS ( P < .0001) and to 0.34 ± 0.29 12 months after PRK ( P < .0001). Mean spherical equivalent decreased from -5.19 ± 4.81 D in the preoperative to -3.38 ± 4.51 D after ICRS ( P < .0001) and to -2.30 ± 2.84 D after PRK ( P = .132). Mean topographic astigmatism decreased from 7.88 ± 2.13 D in the preoperative to 5.47 ± 2.29 D after ICRS ( P < .0001) and to 4.12 ± 2.93 D after PRK ( P = .003). Mean refractive astigmatism decreased from 7.10 ± 1.13 D in the preoperative to 4.61 ± 1.61 D after ICRS ( P < .0001) and to 2.58 ± 1.49 D after PRK ( P < .0001). After PRK, the mean correction index (CI) for corneal astigmatism was 0.77 ± 0.36. The ICRS/PRK combination resulted in a higher CI than ICRS only, both for corneal and refractive astigmatism. 2 eyes (8%) presented clinically significant opacification. Other complications were endothelial rejection (n = 1, 4%), infectious keratitis (n = 1, 4%), and ICRS extrusion after corneal melting (n = 1, 4%). CONCLUSIONS: The association of ICRS and PRK was effective for treating high PKA. This strategy improved visual acuity, spherical equivalent, topographic and refractive astigmatism and resulted in a high CI. Safety questions remain open and must be balanced against benefits.