Quadruple ultrasound, photoacoustic, optical coherence, and fluorescence fusion imaging with a transparent ultrasound transducer.

Ultrasound and optical imagers are used widely in a variety of biological and medical applications. In particular, multimodal implementations combining light and sound have been actively investigated to improve imaging quality. However, the integration of optical sensors with opaque ultrasound transducers suffers from low signal-to-noise ratios, high complexity, and bulky form factors, significantly limiting its applications. Here, we demonstrate a quadruple fusion imaging system using a spherically focused transparent ultrasound transducer that enables seamless integration of ultrasound imaging with photoacoustic imaging, optical coherence tomography, and fluorescence imaging. As a first application, we comprehensively monitored multiparametric responses to chemical and suture injuries in rats' eyes in vivo, such as corneal neovascularization, structural changes, cataracts, and inflammation. As a second application, we successfully performed multimodal imaging of tumors in vivo, visualizing melanomas without using labels and visualizing 4T1 mammary carcinomas using PEGylated gold nanorods. We strongly believe that the seamlessly integrated multimodal system can be used not only in ophthalmology and oncology but also in other healthcare applications with broad impact and interest.

The subjective controllability of exotropia and its effect on surgical outcomes in patients with intermittent exotropia.

BACKGROUND/AIMS: We evaluate the clinical characteristics of intermittent exotropia with controllability and compare surgical outcomes between patients with and without controllability. METHODS: We reviewed the medical records of patients aged 6-18 years with intermittent exotropia who underwent surgery between September 2015 and September 2021. Controllability was defined as the patient's subjective awareness of exotropia or diplopia associated with the presence of exotropia and ability to instinctively correct the ocular exodeviation. Surgical outcomes were compared between patients with and without controllability, with a favorable surgical outcome defined as an ocular deviation between ≤ 10 PD of exotropia and ≤ 4 PD of esotropia at distance and near. RESULTS: Among 521 patients, 130 (25%, 130/521) had controllability. The mean age of onset (7.7 years) and surgery (9.9 years) were higher in patients with controllability than in those without controllability (p < 0.001). The mean control scores of patients with controllability (distance: 1.9, near: 1.5) were lower compared with patients without controllability (distance: 3.0, near: 2.2), reflecting a better level of control. Patients with controllability had a better surgical outcome than those without controllability, as analyzed by log-rank test (p < 0.001). Larger preoperative ocular exodeviation at distance (hazard ratio [HR] = 1.083, confidence interval [CI] = 1.018-1.151, p = 0.012) and near (HR = 1.102, CI = 1.037-1.172, p = 0.002) were significantly related to recurrence in patients with controllability. CONCLUSIONS: Patients with controllability showed better surgical outcomes, later exotropia onset, and better level of control than patients without controllability. Preoperative ocular exodeviation was a significant factor influencing favorable outcomes in patients with controllable exotropia.

Efficacy and safety of 1% and 2% rebamipide clear solution in dry eye disease: a multicenter randomized trial.

BACKGROUND: To evaluate the efficacy of 1% and 2% rebamipide clear solution in the treatment of dry eye disease (DED). METHODS: Two hundred twenty patients with DED were randomly assigned to one of three groups: the 1% rebamipide, 2% rebamipide, or placebo (eye drops containing the same ingredients, except for the active components). Each eye drop was instilled four times daily for 12 weeks. Changes in tear film break-up time (TBUT), corneal and conjunctival staining score, Schirmer 1 test, and the Ocular Surface Disease Index (OSDI) from baseline to 12-week visit between the study groups were compared for efficacy assessment. RESULTS: The mean age of study patients was 43.8±14.2 years. The 1% and 2% rebamipide groups showed greater improvement in TBUT (1.99±1.87 and 2.02±2.21 s) at 12 weeks from baseline than the placebo group (1.25±2.93 s). The 2% rebamipide group showed greater improvement in the corneal staining score (- 3.15±2.00) at 12 weeks from baseline than the placebo group (- 2.85±1.80). The 1% and 2% rebamipide groups showed improvement in Schirmer 1 test (1.27±3.86 and 1.50±4.14 mm) at 12 weeks of treatment, but not the placebo group (0.55±2.99 mm). Both the rebamipide groups and the placebo group showed significantly improved OSDI after treatment for 12 weeks; however, there was no significant difference among the three groups. CONCLUSIONS: 1% and 2% rebamipide clear solutions are an effective therapeutic option for improving TBUT and tear volume, and stabilizing the corneal staining score in DED.

A 1-Year Prospective Comparative Study of Sutureless Flanged Intraocular Lens Fixation and Conventional Sutured Scleral Fixation in Intraocular Lens Dislocation.

PURPOSE: To compare surgical outcomes of sutureless flanged intraocular lens (IOL) fixation and conventional sutured scleral fixation (SF) for secondary IOL implantation in patients with IOL dislocation. METHODS: This is a prospective, comparative cohort study on 103 consecutive patients (103 eyes) with IOL dislocation who underwent vitrectomy with IOL removal and sutured SF (53 eyes) or flanged IOL fixation (50 eyes). Operating time, best-corrected visual acuity (BCVA), refractive difference, IOL tilt and decentration using swept-source anterior segment OCT, and postoperative complications were measured for 12 months. RESULTS: Operating time was significantly shorter for the flanged IOL fixation than for sutured SF (19.4 ± 4.6 vs. 48.9 ± 5.2 min, p < 0.001). BCVA in both groups improved at 1, 3, 6, and 12 months postoperatively (p < 0.05). BCVA in the 2 groups was similar during the 12 months of observation. The refractive difference, IOL tilt, IOL decentration, and incidence of postoperative complications were also not different in the 2 groups. CONCLUSION: Sutured SF and flanged IOL fixation had similar visual outcomes and IOL stability in patients with IOL dislocation. However, the operating time for flanged IOL fixation was less than half that of the sutured SF. This technique is an efficient alternative for treating IOL dislocation.

Simplified Classification of Tear Film Break-Up Patterns and Their Clinicopathological Correlations in Patients With Dry Eye Disease.

PURPOSE: To analyze the pathophysiological differences between patients with dry eye disease (DED) having different tear film break-up patterns (TBUPs). METHODS: This investigative analysis involved 91 eyes of 91 patients with DED who were divided into two groups: those with "dot" break-up pattern (group I) and those with "random" break-up pattern (group II). Clinical severity was evaluated using the Ocular Surface Disease Index (OSDI), Oxford stain score system (OSS) score, and tear film break-up time (TF-BUT). Eighteen patients in group I and 17 patients in group II were selected for sampling of tears and the conjunctiva, and the concentrations of inflammatory cytokines and mucin in the tears and conjunctival tissue were measured. RESULTS: Thirty-seven patients were classified as group I and 54 patients as group II. Patients in group I had a statistically lower TF-BUT and a higher OSS score than those in group II, whereas the OSDI was not statistically different between the groups. The concentrations of interleukin (IL)-6 and IL-8 were statistically higher in group I than those in group II. Impression cytology showed that the expression of IL-1ß and IL-8 was higher in group I, whereas that of other genes was not statistically different. CONCLUSIONS: We were able to clearly classify patients with DED with different TBUPs into two groups, and each group had different clinical and pathophysiological characteristics. In patients with the dot break-up pattern, the disease was strongly associated with ocular surface inflammation, as opposed to that in patients without this pattern.

Retraction Note: Comparison of 0.05% cyclosporine and 3% diquafosol solution for dry eye patients: a randomized, blinded, multicenter clinical trial.

An amendment to this paper has been published and can be accessed via the original article.

Comparison of 0.05% cyclosporine and 3% diquafosol solution for dry eye patients: a randomized, blinded, multicenter clinical trial.

BACKGROUND: This study is aim to compare the clinical effectiveness between the two most prominent dry eye disease (DED)-specific eye drops, 0.05% cyclosporine (CN) and 3% diquafosol (DQ). METHODS: This is a multi-centered, randomized, masked, prospective clinical study. A total of 153 DED patients were randomly allocated to use CN twice per day or DQ six times daily. Cornea and conjunctival staining scores (NEI scale), tear break-up time (TBUT), Schirmer test scores, and ocular surface disease index (OSDI) score were measured at baseline, 4 and 12 weeks after treatment. RESULTS: At 12 weeks after treatment, NEI scaled scores were significantly reduced from the baseline by - 6.60 for CN and - 6.63 for DQ group (all P < 0.0001, P = 0.9739 between groups). TBUT and Schirmer values for CN were significantly improved from the baseline at 4 and 12 weeks (P = 0.0034, P < 0.0001 for TBUT, P = 0.0418, P = 0.0031 for Schirmer test). However, for DQ, TBUT showed significant improvement at 12 weeks only (P = 0.0281). Mean OSDI score differences from the baseline to 12 weeks were improved by - 13.03 ± 19.63 for CN and - 16.11 ± 20.87 for DQ, respectively (all P < 0.0001, P = 0.854 between groups). Regarding drug compliance, the mean instillation frequency of CN was less than that of DQ (P < 0.001). There were no statistically significant intergroup differences in safety evaluation. CONCLUSIONS: The level of improvement regarding NEI, TBUT, and OSDI scores were not significantly different between the two treatment groups. However, with regards to the early improvement of TBUT and patient compliance, patients using CN improved faster and with greater adherence to drug usage than did those treated with DQ. TRIAL REGISTRATION: KCT0002180 , retrospectively registered on 23 December 2016.

Lateral ankle ligament reconstruction using the anterior half of the peroneus longus tendon.

PURPOSE: The purpose of this study was to assess the results of a novel surgical technique for the treatment of chronic lateral ankle instability with attenuated or deficient ligamentous tissue that the modified Broström procedure could not be performed. A lateral ankle ligament reconstruction using the anterior half of the peroneus longus tendon has been performed. METHODS: Thirty-four consecutive patients treated with lateral ankle ligament reconstruction using anterior half of the peroneus longus tendon were enrolled. Median age at surgery was 24 years (range 19-46 years). The clinical and radiologic outcomes were evaluated preoperatively and at a median of 21 months (range 12-51 months) follow-up. RESULTS: The Karlsson-Peterson ankle score significantly improved from 58.2 ± 10.9 points preoperatively to 83.9 ± 7.0 points at the last follow-up. Mechanical stability was achieved. The mean talar tilt angle significantly improved from 15.7° ± 3.5° preoperatively to 4.6° ± 1.7° at the last follow-up, and the mean anterior talar translation significantly improved from 7.3 ± 2.6 mm preoperatively to 4.1 ± 1.7 mm at the last follow-up. Fifteen patients (52%) were very satisfied with the results, nine patients (31%) were satisfied, four patients (14%) were fair, and one patient (3%) was dissatisfied with the results. CONCLUSIONS: Lateral ankle ligament reconstruction using the anterior half of the peroneus longus tendon can be a surgical option for chronic lateral ankle instability with attenuated or deficient ligaments. LEVEL OF EVIDENCE: Case-series, Level IV.

Time-dependent periimplant bone reaction of acidic monomer-treated injection molded zirconia implants in rabbit tibiae.

PURPOSE: The aim of this study was to evaluate and compare the osseointegration of zirconia implants in rabbit tibiae with and without 10-methacryloyloxydecyl dihydrogen phosphate (MDP) treatment. MATERIALS AND METHODS: Twenty-eight rabbits received a total of 112 external hex-type implants made by the powder injection molding technique with and without MDP treatment before installation in the tibiae. The contact angles on the zirconia implants and zirconia discs before and after MDP application were evaluated. Removal torque (RT) and bone-implant contact (BIC) ratios were measured. RESULTS: The MDP treatment markedly enhanced the hydrophilicity and seemed to alter the topography and chemical composition of the implant and disc surface. As the healing time increases, the BIC and RT were increased in both groups. The MDP-treated implants exhibited higher BIC values than the control implants after 2 and 4 weeks of healing. The RT was higher in MDP-treated implants after 2 weeks of healing but not after 4 weeks of healing. CONCLUSION: The 10-MDP treatments made the surface more hydrophilic and enhanced the osseointegration of the implants in the early healing phase.

Peri-implant bone formation of non-thermal atmospheric pressure plasma-treated zirconia implants with different surface roughness in rabbit tibiae.

OBJECTIVES: The aim of this study was to evaluate and compare the osseointegration of powder-injection molded (PIM) zirconia implants in rabbit tibiae with or without He plasma treatment. MATERIAL AND METHODS: Twenty-five rabbits received 4 types of external hex implants with identical geometry in the tibiae: PIM zirconia implants, roughened PIM zirconia implants, plasma-treated PIM zirconia implants, and plasma-treated roughened PIM zirconia implants. The contact angles of the four types of implants were evaluated. Removal torque tests and histomorphometric analyses were performed. RESULTS: The plasma treatment markedly enhanced the hydrophilicity, but did not seem to change the surface topography of the PIM zirconia implants. There were statistically significant differences in the bone-to-implant contact (BIC) ratios, bone volume (BV/TV), and removal torque values (RTQ) among the tested implant types (P < 0.001). The plasma-treated implants exhibited significantly higher BIC and BV/TV values than the untreated implants. However, the removal torque values favored the rough surface. CONCLUSIONS: The He plasma treatments on PIM zirconia implants made the surface more hydrophilic and enhanced the osseointegration of the implants without changing the micro-topography.

Submorphotypes of the maxillary first molar and their effects on alignment and rotation.

INTRODUCTION: The aim of this study was to explore the shape differences in maxillary first molars with orthographic measurements using 3-dimensional virtual models to assess whether there is variability in morphology that could affect the alignment results when treated by straight-wire appliance systems. METHODS: A total of 175 maxillary first molars with 4 cusps were selected for classification. With 3-dimensional laser scanning and reconstruction software, virtual casts were constructed. After performing several linear and angular measurements on the virtual occlusal plane, the teeth were clustered into 2 groups by the method of partitioning around medoids. To visualize the 2 groups, occlusal polygons were constructed using the average data of these groups. RESULTS: The resultant 2 clusters showed statistically significant differences in the measurements describing the cusp locations and the buccal and lingual outlines. The rotation along the centers made the 2 cluster polygons look similar, but there was a difference in the direction of the midsagittal lines. CONCLUSIONS: There was considerable variability in morphology according to 2 clusters in the population of this study. The occlusal polygons showed that the outlines of the 2 clusters were similar, but the midsagittal line directions and inner geometries were different. The difference between the morphologies of the 2 clusters could result in occlusal contact differences, which might be considered for better alignment of the maxillary posterior segment.

The growth trends of Korean adolescents with bialveolar protrusion: a nine year longitudinal cephalometric study.

Bialveolar protrusion and dental crowding seems to have common features in terms of aetiology and treatment method, although they result in different facial profiles and tooth alignment. The aim of this longitudinal study is to determine when children begin to show bialveolar protrusive traits in order to get more clue about the aetiology of bialveolar protrusion. Longitudinal lateral cephalometric data of children followed from 6 to 14 years of age were used. A total of 155 children (81 girls and 74 boys) with showing Class molar relationships at the age of 14 were assigned to either the protrusive group (PG) or the non-protrusive group (NPG), based on 5 cephalometric measurements. The cephalometric measurements of these 2 groups were compared at each age separately in both sexes by independent t-tests. Throughout the entire observation period, there were differences between PG and NPG in both sexes in measurements which were used for classification at 14 years of age. There were differences between sexes in both PG and NPG in several measurements of at several different ages. Individuals with bialveolar protrusive traits at the age of 14 exhibited the signs early in life, at least from the early mixed dentition.

Arthroscopic ankle arthrodesis with intra-articular distraction.

Arthroscopic ankle arthrodesis has shown high rates of union comparable to those with open arthrodesis but with substantially less postoperative morbidity, shorter operative times, less blood loss, and shorter hospital stays. To easily perform arthroscopic resection of the articular cartilage, sufficient distraction of the joint is necessary to insert the arthroscope and instruments. However, sometimes, standard noninvasive ankle distraction will not be sufficient in post-traumatic ankle arthritis, with the development of arthrofibrosis and joint contracture after severe ankle trauma. In the present report, we describe a technique to distract the ankle joint by inserting a 4.6-mm stainless steel cannula with a blunt trocar inside the joint. The cannula allowed sufficient intra-articular distraction, and, at the same time, a 4.0-mm arthroscope can be inserted through the cannula to view the joint. Screws can be inserted to fix the joint under fluoroscopic guidance without changing the patient's position or removing the noninvasive distraction device and leg holder, which are often necessary during standard arthroscopic arthrodesis with noninvasive distraction.

Repositioned versus exchanged flanged intraocular lens fixation for intraocular lens dislocation.

This study aimed to compare the outcomes of flanged intraocular lens (IOL) fixation with new IOL exchange after dislocated IOL removal and repositioned dislocated IOL in patients with IOL dislocation. Eighty-nine eyes that underwent flanged IOL fixation were retrospectively included, with 51 eyes in the exchanged IOL group and 38 eyes in the repositioned IOL group. In both groups, best-corrected visual acuity (BCVA) improved at 1, 3, 6, and 12 months postoperatively and did not differ between the two groups at any of these time points. However, at 1 week postoperatively, BCVA in the repositioned IOL group improved compared with baseline, whereas that in the exchanged IOL group did not. Moreover, there were lesser changes in the corneal endothelial cell density (ECD) and corneal astigmatism in the repositioned IOL group than in the exchanged IOL group. The IOL positions, including IOL tilt and IOL decentration, were not different between the groups. Flanged IOL fixation with new IOL exchange and with repositioned dislocated IOL for patients with IOL dislocation had similar visual outcomes and IOL position. However, the latter had a smaller corneal ECD decrease and astigmatic change. This technique was effective in treating IOL dislocation while minimizing corneal injury.

Real-time in vivo monitoring of intraocular pressure distribution in the anterior chamber and vitreous chamber for diagnosis of glaucoma.

Glaucoma causes irreversible vision loss due to optic nerve damage and retinal cell degeneration. Since high intraocular pressure (IOP) is a major risk factor for glaucoma development, accurate IOP measurement is crucial, especially intravitreal IOP affecting the optical nerve and cells. However, conventional methods have limits in selectively and directly detecting local retina pressure. Here, we present continuous measurements of local IOP values in the anterior chamber and vitreous chamber of living animals using minimally invasive probes with pressure-sensitive transistors. After inducing glaucoma in animal models, we compared the local IOP distribution between normal and glaucomatous eyes. We also compared IOP values detected in the cornea using tonometry measurements. Our findings revealed that glaucoma induced higher IOP in the vitreous chamber than in the anterior chamber, indicating that measuring IOP in the vitreous chamber is key to the glaucoma model. This progress offers future directions for diagnosis and treatment of glaucoma.

In-depth correlation analysis between tear glucose and blood glucose using a wireless smart contact lens.

Tears have emerged as a promising alternative to blood for diagnosing diabetes. Despite increasing attempts to measure tear glucose using smart contact lenses, the controversy surrounding the correlation between tear glucose and blood glucose still limits the clinical usage of tears. Herein, we present an in-depth investigation of the correlation between tear glucose and blood glucose using a wireless and soft smart contact lens for continuous monitoring of tear glucose. This smart contact lens is capable of quantitatively monitoring the tear glucose levels in basal tears excluding the effect of reflex tears which might weaken the relationship with blood glucose. Furthermore, this smart contact lens can provide an unprecedented level of continuous tear glucose data acquisition at sub-minute intervals. These advantages allow the precise estimation of lag time, enabling the establishment of the concept called 'personalized lag time'. This demonstration considers individual differences and is successfully applied to both non-diabetic and diabetic humans, as well as in animal models, resulting in a high correlation.

Peri-implant bone formations around (Ti,Zr)O(2) -coated zirconia implants with different surface roughness.

AIM: The aim of this study was to evaluate and compare the osseointegration in rabbit tibiae of smooth and roughened powder injection moulded (PIM) zirconia implants with or without (Ti,Zr)O2 surface coatings. MATERIAL AND METHODS: Twenty-five rabbits received four types of external hex implants with identical geometry on the tibiae: PIM zirconia implants, roughened PIM zirconia implants, (Ti,Zr)O2 -coated PIM zirconia implants and (Ti,Zr)O2 -coated roughened PIM zirconia implants. The surface characteristics of the four types of implants were evaluated. Removal torque tests and histomorphometric analyses were performed. RESULTS: The (Ti,Zr)O2 coatings substantially changed the surface topography and chemical composition of the both type of PIM zirconia implants. There were statistically significant differences in the bone to implant contact ratios and removal torque values (RT) among the tested implant types (p < 0.001). The histological response favoured the coated surface at smooth PIM zirconia implants. The removal torque values favoured the rough surface whether coated or uncoated. CONCLUSIONS: Within the limit of this study, the (Ti,Zr)O2 coated PIM zirconia implants, both smooth and rough, showed enhanced histological response (bone to implant contact) compared with uncoated ones. On the other hand, the mechanical anchorage (RT) was higher for rough surface implants, coated or uncoated.

Comparison of contamination rates between preserved and preservative-free fluoroquinolone eyedrops.

BACKGROUND: To evaluate the antimicrobial effectiveness of preservative-free fluoroquinolone products compared with benzalkonium chloride containing fluoroquinolones using the challenge test provided by the United States Pharmacopeia (USP) and the in-use test. METHODS: 1. Challenge test: to compare the growth of microorganisms between different fluoroquinolone preparations, four test organisms, including Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Aspergillus niger were chosen among five microorganisms listed by USP 2004. The inoculated products were sampled for microbial survivors at days 7, 14, and 28 following initial inoculation at room temperature. The number of surviving organisms were calculated as a Log10 reduction from the original inocula. 2. In-use test: a total of 100 bottles were collected after instillation of preservative-free fluoroquinolone eyedrops in volunteer patients after 1 week of use. The remaining fluid and tips of the bottles were cultured. Colonies on the plates were counted at the end of the incubation period. All microorganisms were identified by Gram staining and biochemical assays. RESULTS: 1. Challenge test: preservative-free gatifloxacin and levofloxacin demonstrated a lower log reduction against A. niger than preserved fluoroquinolones and preservative-free moxifloxacin at all time points. 2. In-use test: There was no contamination identified on plates inoculated by preservative-free quinolone bottles after 1 week of use in this study. CONCLUSIONS: Physicians should be aware of the lower antifungal preservative effectiveness of some preservative-free fluoroquinolone preparations than preserved ones.

Loop-mediated isothermal amplification targeting 18S ribosomal DNA for rapid detection of Acanthamoeba.

Amoebic keratitis (AK) caused by Acanthamoeba is one of the most serious corneal infections. AK is frequently misdiagnosed initially as viral, bacterial, or fungal keratitis, thus ensuring treatment delays. Accordingly, the early detection of Acanthamoeba would contribute significantly to disease management and selection of an appropriate anti-amoebic therapy. Recently, the loop-mediated isothermal amplification (LAMP) method has been applied to the clinical diagnosis of a range of infectious diseases. Here, we describe a rapid and efficient LAMP-based method targeting Acanthamoeba 18S rDNA gene for the detection of Acanthamoeba using clinical ocular specimens in the diagnosis of AK. Acanthamoeba LAMP assays detected 11 different strains including all AK-associated species. The copy number detection limit for a positive signal was 10 DNA copies of 18S rDNA per reaction. No cross-reactivity with the DNA of fungi or other protozoa was observed. The sensitivity of LAMP assay was higher than those of Nelson primer PCR and JDP primer PCR. In the present study, LAMP assay based on directly heat-treated samples was found to be as efficient at detecting Acanthamoeba as DNA extracted using a commercial kit, whereas PCR was only effective when commercial kit-extracted DNA was used. This study showed that the devised Acanthamoeba LAMP assay could be used to diagnose AK in a simple, sensitive, and specific manner.

Patterns of vertical facial growth in Korean adolescents analyzed with mixed-effects regression analysis.

INTRODUCTION: To understand the growth patterns of skeletal open bite and deepbite, we present observations from 9 years of pure longitudinal data based on lateral cephalometric radiographs using mixed-effects regression model analysis. METHODS: In total, 51 children (14 years old) with extreme values for the ratio of lower anterior facial height to total anterior facial height were assigned to 1 of 2 groups: a skeletal open-bite group (11 boys, 14 girls) or a skeletal deepbite group (14 boys, 12 girls). Measurements of total anterior facial height, upper anterior facial height, lower anterior facial height, total posterior facial height, ramus height, and ratio of lower anterior facial height to total anterior facial height were obtained for all subjects. All data were analyzed and interpreted using a mixed-effects regression model analysis with random effects. RESULTS: From these 4 groups at 14 years old, statistically significant differences were observed between the groups when subjects of the same sex were compared; however, statistical significance was not reached between subjects of opposite sexes in each group. Morphologic differences were clearly evident from the start and became more pronounced with age. There were statistical significances in the initial values and increases with age in all 6 variables except for increases with age in the ratio of lower anterior facial height to total anterior facial height. Statistical significance was also reached for morphologic differences between the annual increases in the ratio of lower anterior facial height to total anterior facial height and lower anterior facial height. In general, individual random variability was high in all variables when compared with the annual changes over time. CONCLUSIONS: Divergent patterns were established early and became more pronounced with age, with anterior facial height dimensions primarily contributing to these differences. Individual variations were so pronounced that caution is recommended for all clinical decisions.