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At least 19 recordsLinked to original sources
PubMed1991

Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study five years after surgery. The Perk Study Group.

In the Prospective Evaluation of Radial Keratotomy (PERK) Study, 793 eyes of 435 patients with 2 to 8 diopters (D) of myopia received a standardized surgery consisting of 8 incisions with a diamond-bladed knife set at 100% of the thinnest paracentral ultrasonic corneal thickness measurement and a diameter of the clear zone of 3.0 to 4.5 mm; 97 eyes (12%) received an additional 8 incisions. There were 757 eyes (95%) followed for 3 to 6.3 years. After surgery, uncorrected visual acuity was 20/40 or better in 88% of eyes. The refractive error was within 1 D of emmetropia for 64% of eyes; 19% were myopic and 17% were hyperopic by more than 1 D. Between 6 months and 5 years after surgery, 22% of the eyes had a refractive change of 1 D or more in the hyperopic direction. For 25 eyes (3%) there was a loss of 2 or more lines of best spectacle-corrected visual acuity.

Adult↗
PubMed1989

Accuracy and reproducibility of KeraScanner analysis in PERK corneal topography. PERK Study Group.

The measurement of the corneal radius of curvature centrally and in the corneal periphery is exceedingly difficult because of variables in photography and data acquisition. We present a technique of Automated image scanning of corneal photographs which provides a more accurate and reproducible analysis of the paracentral corneal contour. We analyzed the sources of error of corneal topography measurement. CorneaScope photographs of calibration balls were generated by each Prospective Evaluation of Radial Keratotomy (PERK) Surgical Center. The 90% confidence intervals for individual ring-radial positions on the 8.00 and 10.00 mm balls were 7.91 to 8.09 mm and 9.89 to 10.11 mm respectively. Our isopter method of analysis for clinical comparison averages all eight radii of curvature for each CorneaScopef ring. This isopter technique reduces the corresponding 90% confidence intervals to 7.96 to 8.03 and 9.95 to 10.06 mm. The measurement variability of a 10 mm calibration ball decreased in the following order: calibration ball positioning, scanner personnel, photograph movement between scans, and nonrepositioned scanning. Photographs of calibration balls demonstrate +/- 4 microns of measurement resolution and patient corneal photographs may be evaluated to +/- 40 microns. This automated scanning system provides consistent data when digitizing keratographs.

Biometry↗
PubMed1990

Results of the Prospective Evaluation of Radial Keratotomy (PERK) Study 4 years after surgery for myopia. Perk Study Group.

The Prospective Evaluation of Radial Keratotomy Study is a nine-center clinical trial of a surgical technique to reduce simple myopia by making incisions in the cornea. There were 435 patients (one eye per patient is reported) enrolled in the study with a 91% follow-up rate at 4 years after surgery. After surgery, uncorrected visual acuity was 20/40 or better in 76% of eyes. Fifty-five percent of the eyes had a refractive error within +/- 1.00 diopter; 28% were undercorrected, and 17% were overcorrected by more than 1.00 D. The width of the prediction 90% interval for the refractive change was 4.42 D, indicating a lack of predictability. The refractive error was not stable in some eyes; between 6 months and 4 years after surgery, 23% of eyes had a continued effect of the surgery of more than 1.00 D. For 323 patients with both eyes operated on, 64% stated they wore no optical correction. There were few serious complications. Eleven eyes (3%) lost two or three lines of best corrected visual acuity. Two eyes developed delayed bacterial keratitis without significant loss in best corrected visual acuity.

Adult↗
PubMed2026

Endothelial PERK restricts lymphoid regeneration by reducing DLL4-NOTCH3 signaling at the Pre-B niche.

Delayed immune recovery after hematopoietic stem cell (HSC) transplantation is associated with a poor clinical outcome. We study the role of unfolded protein response (ER stress) in hematopoietic regeneration within the bone marrow (BM) microenvironment. We reveal that BM endothelium PERK activation is a prominent feature of patients with leukemia and is a hallmark response in mice following ionizing irradiation. Ablating endothelial Perk boosts NOTCH ligand DLL4 expression and promotes DLL4-dependent early HSC and B progenitor regeneration. Single-cell analysis reveals that endothelial DLL4 activates NOTCH3 expressed by mesenchymal stroma cells, and that the PERK-DLL4 axis coordinates the regulation of lymphoid commitment. NOTCH3 is critical for the upregulation of IL7 following irradiation and the expansion of lymphoid progenitors. These findings not only unveil an ER stress-controlled vascular-stroma signaling mechanism in regenerative hematopoiesis but also highlight PERK blockade as a promising strategy to improve immune recovery after myeloablative transplantation.

CP: cell biology↗
PubMed2026

Schisantherin B mitigates cisplatin-induced ototoxicity by modulating the CNPY2-PERK/CHOP signaling axis.

Irreversible cisplatin-induced hearing loss (CIHL) is a refractory chemotherapy-related adverse effect with limited clinical treatments. Schisantherin B (STB), a lignan isolated from Schisandra chinensis, is widely recognized for its neuroprotective properties, while its role in auditory injury remains unclear. Herein, we found that STB alleviated cisplatin-induced ototoxicity in House Ear Institute Organ of Corti 1 (HEI-OC1) cells and guinea pig models, protecting cochlear hair cells, synaptic ribbons and spiral ganglion neurons, and partially restoring auditory brainstem response (ABR) thresholds. Furthermore, combined drug affinity responsive target stability (DARTS) assay, the cellular thermal shift assay (CETSA), and the surface plasmon resonance (SPR) assay, we confirmed STB directly binds to the canopy FGF signaling regulator 2 (CNPY2), a key initiator of endoplasmic reticulum (ER) stress. Notably, consistent dual in vitro and in vivo validation confirmed that STB exerts no regulatory effect on CNPY2 protein abundance, yet suppressed the downstream Protein kinase R-like endoplasmic reticulum kinase / C/EBP homologous protein (PERK/CHOP) signaling cascade and ER stress-mediated apoptosis. Moreover, molecular docking and co-immunoprecipitation (co-IP) validated the physical binding of STB to CNPY2 and the endogenous interaction between CNPY2 and PERK. Additionally, CNPY2 overexpression and shRNA knockdown further verified this functional relationship. Integrated proteomic and transcriptomic analyses showed STB partially reversed cisplatin-triggered inflammation and excessive ER stress. Collectively, our results suggest STB may serve as a potential otoprotective agent. The CNPY2-PERK/CHOP axis is closely linked to cisplatin-induced cochlear damage and offers a feasible target for intervention against CIHL. Abbreviations: CIHL, cisplatin-induced hearing loss; STB, Schisantherin B; HEI-OC1, house ear institute organ of corti 1; ABR, auditory brainstem response; DARTS, drug affinity responsive target stability; CETSA, cellular thermal shift assay; SPR, surface plasmon resonance; CNPY2, canopy FGF signaling regulator 2; ER, endoplasmic reticulum; PERK, protein kinase R-like endoplasmic reticulum kinase; CHOP, C/EBP homologous protein; co-IP, co-immunoprecipitation; STA, Schisantherin A; STC, Schisantherin C; dB SPL, decibels sound pressure level; EDTA, ethylenediaminetetraacetic acid; dB SPL, decibels sound pressure level; SGN, spiral ganglion neuron; IHCs, inner hair cells; OHCs, outer hair cells; CCK-8, Cell Counting Kit-8; OD, optical density; ODb, blank sample, ODc, control sample; NC, negative control; PVDF, polyvinylidene difluoride; RT, room temperature; LC-MS/MS, liquid chromatography tandem mass spectrometry; MS, mass spectrometry; DMSO, dimethyl sulfoxide; KDs, equilibrium dissociation constants; SP, standard precision; SEM, standard error of the mean; HSD, honestly significant difference; Ctrl, control group; CV, cell viability; Kd, dissociation rate constant; Ka, association rate constant; STS, sodium thiosulfate; UPR, unfolded protein response; BLB, blood-labyrinth barrier.

Apoptosis↗
PubMed2025

MLL1 downregulation drives hair cell ferroptosis via mitochondrial and endoplasmic reticulum stress mechanisms through PERK-eIF2α-ATF4-Chop and PI3K/Akt-Lrp1 signaling pathway.

BACKGROUND: Sensorineural hearing loss is characterized by irreversible hair cell (HC) degeneration. Ferroptosis, which is marked by the accumulation of reactive oxygen species and elevated levels of lipid peroxidation products, has been shown to contribute to drug-mediated auditory impairment. This study aimed to elucidate the role of mixed-lineage leukemia 1 (MLL1) in HC survival in the auditory system. METHODS: The HEI-OC1 auditory cell line and postnatal cochlear explants were evaluated using MM-102, a specific MLL1 histone methyltransferase inhibitor. Western blotting, quantitative polymerase chain reaction, electron microscopy, and immunofluorescence were used to elucidate the role of MLL1 in regulating ferroptosis in HC injury. RNA sequencing (RNA-seq) was used to analyze the molecular mechanisms of MLL1 intervention in HC injury from an epigenetic perspective. RESULTS: Our findings demonstrated that immunofluorescence staining revealed a crucial role of MM-102 in promoting intracellular accumulation of lipid peroxides and ferrous ions. Subsequent analysis showed MLL1 downregulation-induced mitochondrial dysfunction and endoplasmic reticulum (ER) stress, with transmission electron microscopy imaging confirming ultrastructural alterations in mitochondria and ER. Mechanistic investigations identified the PERK-eIF2α-ATF4-Chop signaling axis as the regulatory pathway, evidenced by Western blotting quantification of phosphorylated PERK (p-PERK), ATF4, and Chop levels. RNA-seq analysis revealed 741 differentially expressed genes (335 upregulated and 406 downregulated). Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis specifically highlighted significant enrichment of the PI3K/Akt-Lrp1 pathway, with corresponding activation patterns of phospho (p)-Akt and Lrp1 confirmed through Western blotting analysis. CONCLUSIONS: MLL1 downregulation initiates ferroptosis in cochlear HCs. This process is intrinsically associated with the activation of mitochondrial dysfunction and ER stress. The study highlights the importance of MLL1 in HC survival, suggesting its potential as a therapeutic target for treating hearing loss.

Endoplasmic Reticulum Stress↗
PubMed1991

Corneal topography as a predictor of refractive change in the prospective evaluation of radial keratotomy (PERK) study.

The first operated eyes of 435 patients undergoing radial keratotomy in the Prospective Evaluation of Radial Keratotomy (PERK) study were evaluated by photokeratography to document the preoperative and postoperative corneal shape. We determined by regression analysis and analysis of variance that the corneal shape preoperatively improved the prediction of the corneal shape 6 months postoperatively in the 3-mm-clear-zone population. The reduction of myopia in all 435 eyes ranged from 1.25 to 9.75 diopters. We studied the effect of the preoperative corneal shape on this variability in the outcome of the surgery using rings 2 and 7 on photokeratography and corneal diameter. In the 3-mm-clear-zone group, eyes with flat prolate corneas had a greater reduction in myopia (4.65 D); those with steeper, more spherical corneas had less reduction in myopia (3.48 D). In addition, eyes with a 3-mm clear zone and flat central corneas alone (8.0 mm = 42.19 D) flattened approximately 0.75 D more than those with steep central corneas (7.0 mm = 48.21 D). In the 3.5-mm and 4.0-mm clear zone groups, the change in corneal curvature was not related to the preoperative curvature. A stepwise regression analysis of the 151 eyes in the 3.0-mm-clear-zone population demonstrated the following predictive equation for radial keratotomy; change in cycloplegic refraction = -14.55 + [-2.097 x average ring-2 radius] + [3.605 x average ring-7 radius] + [0.69 x horizontal corneal diameter] + [0.079 x age] + [-0.379 x spherical equivalent cycloplegic refraction]. There was a 1.17-D observed difference in the effect of radial keratotomy between those eyes with a steep/steep corneal topography (7.2% of the 3.0-mm-clear-zone population) and the flat/flat topography (29% of the 3.0-mm-clear-zone PERK population). A knowledge of corneal topography provides an additional tool for understanding the operative variability of radial keratotomy.

Cornea↗
PubMedDate not supplied

Symmetry of refractive and visual acuity outcome in the Prospective Evaluation of Radial Keratotomy (PERK) study.

In the Prospective Evaluation of Radial Keratotomy (PERK) study, the symmetry of refractive and visual acuity outcome was analyzed in 269 patients with bilateral radial keratotomy with a single operation in each eye. Patients were required to wait 1 year after surgery on the first eye before having surgery on the second eye. At 1 year after surgery on the second eye, 98% of patients had 3.00 diopters or less difference between their two eyes in the spherical equivalent of the cycloplegic refraction (100% before surgery), and 96% of patients had 3.00 D or less difference between their two eyes in the amount of refractive power in the vertical meridian (100% before surgery). Thus, surgically induced refractive anisometropia was not a major complication in the PERK study. However, 14% of patients had four to eight Snellen lines difference in the uncorrected visual acuity between their two eyes (1% before surgery), emphasizing that induced asymmetry of refraction is a potential clinical problem for some patients.

Adult↗
PubMed1986

Reported satisfaction, fluctuation of vision, and glare among patients one year after surgery in the Prospective Evaluation of Radial Keratotomy (PERK) Study.

We studied satisfaction with the results of radial keratotomy one year after surgery on one eye as reported by 354 patients in the Prospective Evaluation of Radial Keratotomy (PERK) Study. We measured satisfaction using an index based on ten questions that were part of a longer psychometric questionnaire. Patients were generally satisfied with the results of radial keratotomy-48% were very satisfied, 42% were moderately satisfied, and 10% were dissatisfied. A lot of trouble with fluctuating vision was reported by 12% of patients before surgery and by 34% one year after surgery; 17% reported a lot of trouble with glare both before surgery and one year after surgery. The three major factors that influenced satisfaction were uncorrected visual acuity, residual refractive error, and subjective daily fluctuation in vision. A multiple regression equation that incorporated these three variables, glare, and patient sex was able to predict only 46% of the variance in patient satisfaction.

Adult↗
PubMed1987

Factors affecting outcome and predictability of radial keratotomy in the PERK Study.

The Prospective Evaluation of Radial Keratotomy (PERK) study used a standardized surgical technique that included a central clear zone with a diameter of 4.0, 3.5, or 3.0 mm. Multiple regression analysis of the outcome in one eye from each of 411 patients disclosed that the diameter of the central clear zone, patient age, and depth of the incision scar were the major factors affecting the change in refraction one year after surgery. Preoperative factors examined that did not have a significant influence on the outcome were sex, average central keratometric power, corneal thickness, corneal diameter, intraocular pressure, and ocular rigidity. The predictability of radial keratotomy, ie, the precision with which the outcome can be estimated, was measured by the 90% confidence interval for the change in refraction based on the regression equation. The width of this interval within each clear zone group was as follows: 4.0 mm, 2.49 diopters; 3.5 mm, 3.38 D; 3.0 mm, 4.12 D. For all 411 eyes, the 90% confidence interval was approximately 3.50 D wide. Thus, the surgeon could be 90% certain that an individual patient's refraction would be within 1.75 D of the predicted value one year after surgery.

Age Factors↗
PubMed1987

Relationship between refractive error and visual acuity in the Prospective Evaluation of Radial Keratotomy (PERK) Study.

As part of the Prospective Evaluation of Radial Keratotomy (PERK) study, we examined the relationship between post-operative refractive error and visual acuity without correction. We included 394 eyes (one eye per patient) with refractive errors ranging from -3.00 to +3.00 diopters one year after radial keratotomy. Within each 1-D range of the spherical equivalent of the refractive error, the visual acuity spanned five to ten Snellen lines. For visual acuities of 20/16 to 20/50, the refractive error spanned 3 to 5 D. Additionally, operated eyes had a better average uncorrected visual acuity than unoperated eyes with a similar refractive error. Within the narrow range of refraction between -2.00 and -2.50 D, the mean uncorrected visual acuity was 20/125 for 56 unoperated eyes and 20/63 for 29 operated eyes, a difference of three Snellen lines.

Adult↗
PubMed2026

Genome-wide characterization of the tomato PERK gene family and its expression profiling under abiotic stresses.

UNLABELLED: This study presents the first systematic genome-wide characterization of the proline-rich extensin-like receptor kinases (PERK) gene family in tomato (Solanum lycopersicum) and their transcriptional responses under abiotic stresses. Using the latest SL4.0/ITAG4.0 genome assembly, we identified six SlPERK genes, all harboring the conserved Ser/Thr protein kinase domain. Evolutionary and structural analyses revealed strong purifying selection (Ka/Ks&#x2009;<&#x2009;1), distinct exon-intron organizations, and the presence of stress- and hormone-responsive cis-regulatory elements in their promoters. Furthermore, post-transcriptional regulation by 57 miRNAs and complex protein-protein interaction networks were predicted. To validate their stress-responsive roles, two tomato cultivars (GMOTL-1 and Roma) were subjected to cold, heat, and salinity treatments. Quantitative RT-PCR analysis revealed cultivar-specific expression dynamics: SlPERK4 exhibited strong transient induction under cold and heat stress, while SlPERK6 was highly responsive to salinity. Notably, the GMOTL-1 cultivar displayed significantly higher and broader stress-responsive expression profiles compared to Roma, indicating a potential role of these SlPERK genes in cultivar-specific stress tolerance. These findings provide a comprehensive genomic resource and establish a critical foundation for the functional validation and molecular breeding for stress-resilience tomato cultivars. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13205-026-05044-y.

Abiotic stress↗
PubMed1985

Results of the prospective evaluation of radial keratotomy (PERK) study one year after surgery.

The Prospective Evaluation of Radial Keratotomy (PERK) study is a nine-center, self-controlled clinical trial of a standardized technique of radial keratotomy in 435 patients who had physiologic myopia with a preoperative refraction between -2.00 and -8.00 diopters. The surgical technique consisted of eight incisions using a diamond micrometer knife with blade length determined by intraoperative ultrasonic pachymetry and the diameter of central clear zone determined by preoperative refraction. At one year after surgery, myopia was reduced in all eyes; 60% were within +/- 1.00 diopter of emmetropia; 30% were undercorrected and 10% were overcorrected by more than 1.00 diopter (range of refraction, -4.25 to +3.38 D). Uncorrected visual acuity was 20/40 or better in 78% of eyes. The operation was most effective in eyes with a refraction between -2.00 and -4.25 diopters. Thirteen percent of patients lost one or two Snellen lines of best corrected visual acuity. However, all but three eyes could be corrected to 20/20. Ten percent of patients increased astigmatism more than 1.00 diopter. Disabling glare was not detected with a clinical glare tester, but three patients reduced their driving at night because of glare. Between six months and one year, the refraction changed by greater than 0.50 diopters in 19% of eyes.

Adult↗
PubMed1986

Comparison of ultrasonic corneal thickness measurements before and during surgery in the prospective evaluation of Radial Keratotomy (PERK) Study.

Central corneal thickness, determined by an ultrasonic pachymeter, was studied in one eye each of 395 patients enrolled in the Prospective Evaluation of Radial Keratotomy (PERK) Study, to determine the changes in central corneal thickness between preoperative and intraoperative measurements. There was no statistical difference between the preoperative and the intraoperative measurement. However, 9.4% of the corneas were 0.03 to 0.08 mm thinner intraoperatively and 3.3% were 0.03 to 0.06 mm thicker intraoperatively, indicating that clinically meaningful changes in corneal thickness occurred between the preoperative and intraoperative measurements in some eyes. We conclude that the most reliable way to use ultrasonic pachymetry readings to set the length of the knife blade for radial keratotomy surgery is to measure the corneal thickness intraoperatively.

Cornea↗
PubMed1986

Diurnal change in refraction, corneal curvature, visual acuity, and intraocular pressure after radial keratotomy in the PERK Study.

Selected patients who complained of fluctuating visual acuity in the Prospective Evaluation of Radial Keratotomy (PERK) Study were examined before 8:00 a.m. and after 7:00 p.m. on the same day to determine diurnal change in uncorrected visual acuity, best corrected visual acuity, manifest refractive error, average central keratometric power, and intraocular pressure. Sixty-three operated eyes were examined at three months, while 46 operated and 40 unoperated contralateral eyes were examined at one year after radial keratotomy. One year after surgery, 42% of the operated eyes had an increase in minus power of the manifest refraction of 0.50 to 1.25 diopters, 26% of the eyes changed their uncorrected visual acuity by 2 to 4 Snellen lines, and 35% of the operated eyes showed central steepening of the cornea by 0.50 to 1.25 diopters. These changes in the operated eyes at one year were similar to the changes at three months. Minimal diurnal changes occurred in the unoperated eyes at one year. Only 11% of the unoperated eyes changed their manifest refraction by 0.50 to 1.00 diopters, none changed their uncorrected visual acuity by 2 to 4 Snellen lines, and only one of the unoperated eyes changed its central keratometric power by 0.50 diopters. This study documents that many patients who experience diurnal fluctuation of vision have steepening of the cornea and an increase in the minus power of their refraction during the day.

Biomechanical Phenomena↗
PubMed1987

Three-year results of the Prospective Evaluation of Radial Keratotomy (PERK) Study.

The Prospective Evaluation of Radial Keratotomy (PERK) study is a nine-center clinical trial of a standardized technique of radial keratotomy in 435 patients who had simple myopia with a preoperative refractive error between -2.00 and -8.00 diopters (D). The authors report results for one eye of each patient. The surgical technique consisted of eight incisions using a diamond micrometer knife with the blade length determined by intraoperative ultrasonic pachymetry and the diameter of the central clear zone determined by the preoperative refractive error. At 3 years after surgery, 58% of eyes had refractive error within 1.00 D of emmetropia; 26% were undercorrected and 16% were overcorrected by more than 1.00 D. Uncorrected visual acuity was 20/40 or better in 76% of eyes. The operation was more effective in eyes with a preoperative refractive error between -2.00 and -4.37 D. Between 1 and 3 years after surgery, the refractive error changed by 1.00 D or more in 12% of eyes, indicating a lack of stability in some eyes. In the 435 eyes, there was a small number of complications including six eyes that lost two or three lines of best-corrected acuity, 16 that experienced vascularization of the incisions, 2 that had delayed bacterial keratitis, and 4 that had recurrent epithelial erosions.

Follow-Up Studies↗
PubMed1988

Morning-to-evening change in refraction, corneal curvature, and visual acuity 2 to 4 years after radial keratotomy in the PERK Study.

The authors previously reported morning-to-evening changes in ophthalmic measurements at 3 months and at 1-year after radial keratotomy in a self-selected group of patients in the Prospective Evaluation of Radial Keratotomy (PERK) study. Fifty-two patients included in the earlier study were examined again between 2 1/2 and 4 years after surgery before 10:00 AM and after 5:30 PM on the same day to determine if the changes persisted beyond 1 year after surgery. Between the morning and evening examinations, 31% of the eyes had an increase in minus spherical equivalent power of the manifest refraction of 0.50 to 1.50 diopters; 12% had a change in cylinder power of 0.50 to 1.00 D; 19% had a decrease in uncorrected visual acuity of two to five Snellen lines; and 29% showed central corneal steepening by 0.50 to 1.00 D. Thus, in some patients, morning-to-evening fluctuation persisted until 2 1/2 to 4 years after radial keratotomy.

Circadian Rhythm↗
PubMed1988

The evaluation of corneal endothelial permeability in PERK study patients.

Sixteen patients enrolled in the PERK study were evaluated by fluorophotometry 24 hours or six months following radial keratotomy. A comparison of eyes operated and not operated upon showed that endothelial permeability was not significantly altered 24 hours and six months after surgery. Aqueous humour flow rates and anterior chamber elimination coefficients were significantly higher 24 hours after surgery in the eyes operated on than in those not operated on. Six months after surgery there was no longer a significant difference in these factors. The increase in aqueous humour flow rates 24 hours after surgery may represent a subclinical breakdown in the blood-aqueous barrier.

Adult↗