iCare® Home vs Goldmann applanation tonometry: Agreement of methods and comparison of inter-observer variation at a tertiary eye centre.

Purpose: To investigate whether the inter-observer variation is similar between the Goldmann applanation tonometer used by healthcare staff and the iCare® Home tonometer used by glaucoma patients, volunteers and healthcare staff. Methods: Sixty-one participants were recruited to the study, including 24 glaucoma patients. Seven participants were excluded. For each participant, intraocular pressure (IOP) was measured on the same occasion by two different healthcare staff using GAT as well as by a healthcare staff and the participant using the iCare® Home tonometer. Results: Seventy-two per cent of iCare® measurements were within 3 mmHg of the GAT measurements. There was a statistically significant difference between the trainers' measurements made with iCare® Home and those made with GAT (p < 0.001), as well as between the GAT measurements made by trainers and those made by extra personnel (p = 0.017). The strongest correlation was between iCare® Home participants' and trainers' measurements (0.934). The correlation between different users with GAT was lower (0.769). The inter-user agreement was excellent for iCare® Home users (95% CI 0.93, ranging from 0.880 to 0.959) and moderate for GAT users (95% CI 0.741, ranging from 0.558 to 0.849). Conclusion: Our study found that tonometry with iCare® Home has similar or less inter-user variation compared with GAT.

Impact of self-tonometry on glaucoma treatment decision.

PURPOSE: The aim of this study was to examine the impact of self-tonometry on clinicians' decision in glaucoma treatment. MATERIALS AND METHODS: Medical records of 133 patients who had performed self-tonometry using iCare® Home between January and December 2019 were retrospectively reviewed. Inclusion criteria were as follows: age over 18 years, all types of glaucoma, as well as ocular hypertension and glaucoma suspect, compliance with tonometer manufacturer's recommendations and monitoring over at least 2 days. The data consisted of age, gender, diagnosis, visual field index, rate of progression and type of treatment pre- and post-intraocular pressure (IOP) phasing. The following IOP measurements were used to calculate the mean and maximum IOP, and range over each day and consecutive days: Goldmann applanation tonometry (GAT) measurements from referral and training visits and iCare® Home measurements made by the trainers and the patients themselves. A total of 90 patients were included. RESULTS: Clinicians were satisfied with the actual treatment in 54.4% of the cases. There was a statistically significant difference between the clinicians' decision to maintain same treatment or to escalate therapy for all the mean and maximum IOPs measured on each single day and over a 2- or 3-day period (p < 0.002). CONCLUSION: Our results suggest that the presence of high IOP values obtained with self-tonometry supports an intensification of glaucoma treatment. Self-tonometry provides clinicians with an important complement for clinical decision-making, and under- or over-treatment may be avoided for the benefit of patients.

Mitochondrial Targeting and pH-Responsive Nanogels for Co-Delivery of Lonidamine and Paclitaxel to Conquer Drug Resistance.

Multidrug resistance (MDR) is one of the leading causes of the failure of cancer chemotherapy and mainly attributed to the overexpression of drug efflux transporters in cancer cells, which is dependent on adenosine triphosphate (ATP). To overcome this phenomenon, herein, a mitochondrial-directed pH-sensitive polyvinyl alcohol (PVA) nanogel incorporating the hexokinase inhibitor lonidamine (LND) and the chemotherapeutic drug paclitaxel (PTX) was developed to restore the activity of PTX and synergistically treat drug-resistant tumors. The introduction of 2-dimethylaminoethanethiol (DMA) moiety into the nanogels not only promoted the drug loading capacity but also enabled the lysosomal escape of the nanogels. The subsequent mitochondrial targeting facilitated the accumulation and acid-triggered payload release in the mitochondria. The released LND can destroy the mitochondria by exhausting the mitochondrial membrane potential (MMP), generating reactive oxygen species (ROS) and restraining the energy supply, resulting in apoptosis and susceptibility of the MCF-7/MDR cells to PTX. Hence, the nanogel-enabled combination regimen of LND and PTX showed a boosted anti-tumor efficacy in MCF-7/MDR cells. These mitochondrial-directed pH-sensitive PVA nanogels incorporating both PTX and LND represent a new nanoplatform for MDR reversal and enhanced therapeutic efficacy.

Cascade-Responsive Hierarchical Nanosystems for Multisite Specific Drug Exposure and Boosted Chemoimmunotherapy.

The precise delivery of multiple drugs to their distinct destinations plays a significant role in safe and efficient combination therapy; however, it is highly challenging to simultaneously realize the targets and overcome the intricate biological hindrances using an all-in-one nanosystem. Herein, a cascade-responsive hierarchical nanosystem containing checkpoint inhibitor anti-PD-L1 antibody (αPD-L1) and paclitaxel (PTX) is developed for spatially programed delivery of multiple drugs and simultaneously overcoming biological pathway barriers. The hierarchical nanoparticles (MPH-NP@A) are composed of pH-sensitive hyaluronic acid-acetal-PTX prodrugs (HA-ace-PTX(SH)) chaperoned by αPD-L1 and metalloproteinase-9 (MMP-9)-responsive outer shells, which could be fast cleaved to release αPD-L1 in the tumor microenvironment (TME). The released αPD-L1 sequentially synergizes with PTX released in the cytoplasm for boosted chemoimmunotherapy due to direct killing of PTX and intensified immune responses through immunogenic cell death (ICD) as well as suppression of immune escape by blocking the PD-1/PD-L1 axis. The in vitro and in vivo studies demonstrate that MPH-NP@A evokes distinct ICD, enhanced cytotoxic T lymphocytes infiltration, as well as significant tumor inhibition, thus providing a promising therapeutic nano-platform for safe and efficient combination therapy.

European real-world data about the use of a new delivery system containing a preservative-free multi-dose glaucoma treatment.

BACKGROUND: Glaucoma treatments are mostly presented in uni-dose or multi-dose format. A certain number of patients with visual acuity and dexterity problems may have problems in instilling eye drops. AIM: To assess patient satisfaction and ease of use of a preservative-free glaucoma treatment (dorzolamide/timolol) in a new and innovative patented multi-dose delivery system. METHODS: Retrospective, international, multicentre, non-interventional study in 788 adult patients using a multi-dose delivery system for at least 28 days. RESULTS: Mean patient age was 68.1 ± 12.1 years. Mean duration of multi-dose delivery system use was 132.1 ± 125.1 days; 66.5% of the patients previously used multi-dose and 33.5% uni-dose delivery systems (n = 734); 78.3% of the patients were satisfied or very satisfied with the multi-dose delivery system. A significant majority (all p ≤ 0.045) of patients with a QuickDash® score between [0 to 25[ (66.4%, n = 211) and [50 to 75[ (81.8%, n = 11) rated multi-dose delivery system as easy or very easy to open and significantly more subjects in the [0 to 25[ (72%) score group rated multi-dose delivery system as being better or much better than their previous device (n = 211). Significantly (all p < 0.01) more subjects with available visual acuity results rated multi-dose delivery system as good, better or much better than their previous dispensing device. CONCLUSION: The tested multi-dose delivery system was highly accepted. It is, therefore, suitable for glaucoma patients with decreased visual acuity and/or dexterity problems. Further studies may be necessary to assess the easiness of use of this easy-to-grip delivery system.

Characteristics and evaluation of the effectiveness of monitoring and control measures for the first 69 Patients with COVID-19 from 18 January 2020 to 2 March in Wuxi, China.

BACKGROUND: The Coronavirus disease (COVID-19) has caused 91,305 confirmed cases and 4746 deaths in China by 13:50 on October 11, 2020. We analyzed data on 69 infections in Wuxi to describe the disease's characteristics, to analyze factors of cases clinical outcome and to evaluate the prevention and control measures. METHODS: The demographic characteristics, exposure history, time indicators and propagation dynamics in Wuxi were collected. RESULTS: The clinical severity of cases was mostly mild and normal (75.36 %). Aging (relative risk [RR] = 1.04, 95 % confidence interval [CI]: 1.001-1.08) and fever (RR = 10.33, 95 %CI: 2.75-38.78) were risk factors for disease severity. The mean incubation period was estimated to be 4.77 days (95 % CI: 3.61-5.94), with a mean serial interval of 6.31 days (95 % CI: 5.12-7.50). The controlled reproduction number was estimated to be 1.12 (95 %CI: 0.71-1.69). CONCLUSIONS: The incidence of COVID-19 in Wuxi has turned into a lower level, suggesting the early prevention and control measures have achieved effectiveness. Aging and fever of initial symptom were risk factors for severe clinical outcome. The family clusters provided further clues of the risk factors for COVID-19 transmission.

A cluster of the Corona Virus Disease 2019 caused by incubation period transmission in Wuxi, China.

BACKGROUND: The infectivity and transmission capacity of COVID-2019 cases during the incubation period are not very clear. The manuscript described a cluster to provide information for research on incubation period infection. METHODS: We collected the required data from "Public Health Emergency Reporting Management Information System", epidemiological questionnaires for the cases, and laboratories. RESULTS: The cluster involved four generations, each of which was transmitted to the next generation during the incubation period. The time was 2-7 days, 6-7days, 3-8 days and 9 days prior to onset. As of March 11, the fourth-generation cases had no symptoms. Combined with the epidemiological data, we inferred that the source of the cluster was caused by the first-generation, who contacted with more than ten Wuhan people during the annual meeting from January 15 to 16. Two cases in this cluster were tested positive again during isolation and observation after discharge. CONCLUSIONS: We determined incubation period was infectious, and confirmed that it was contagious 9 days before the onset. The patients who were discharged might need to be observed for a period of time. This study was useful for the practical work, such as in the investigation of close contacts.

Tumor localization of oncolytic adenovirus assisted by pH-degradable microgels with JQ1-mediated boosting replication and PD-L1 suppression for enhanced cancer therapy.

Oncolytic therapy is a fast-developing cancer treatment field based on the promising clinical performance from the selective tumor cell killing and induction of systemic antitumor immunity. The virotherapy efficacy, however, is strongly hindered by the limited virus propagation and negative immune regulation in the tumor microenvironments. To enhance the antitumor activity, we developed injectable pH-degradable PVA microgels encapsulated with oncolytic adenovirus (OA) by microfluidics for localized OA delivery and cancer treatments. PVA microgels were tailored with an OA encapsulation efficiency of 68% and exhibited a pH-dependent OA release as the microgel degradation at mildly acidic conditions. PVA microgels mediated fast viral release and increased replication in HEK293T and A549 cells at a lower pH, and the replication efficiency could be further reinforced by co-loading with one BET bromodomain inhibitor JQ1, inducing significant cytotoxicity against A549 cells. An in vivo study revealed that OA release was highly located at the tumor tissue assisted by PVA microgels, and the OA infection was also enhanced with the addition of JQ1 treatment, meanwhile greatly inhibiting the PD-L1 expression to overcome the immune suppression. OA/JQ1 co-encapsulated injectable microgels exhibited a superior in vivo antitumor activity on the A549 lung tumor-bearing mice by the combination of inhibited proliferation, amplified oncolysis, and potential immune regulation.

Tumor-Adhesive and pH-Degradable Microgels by Microfluidics and Photo-Cross-Linking for Efficient Antiangiogenesis and Enhanced Cancer Chemotherapy.

Tumor angiogenesis with the vascular network formation provides nutrition and oxygen for cancer cells, promoting the proliferation and metastasis of malignant tumors. Bevacizumab (Bev) as an efficient antiangiogenic antibody is able to normalize the tumor vasculature with better blood flow and reduced interstitial fluid pressure, allowing drugs with more uniform distribution and deeper penetration into the tumor; however, it is highly difficult to realize the simultaneous delivery of Bev and anticancer drugs localized at the tumor tissue. Here, we prepared tumor-adhesive and pH-degradable poly(vinyl alcohol) (PVA) microgels for tumor-localized delivery of Bev and docetaxel (DTX), to achieve efficient antiangiogenesis and enhanced cancer chemotherapy. PVA microgels (∼200 µm) decorated with tissue-adhesive dopamine (DA) moieties were fabricated by a combination of high-throughput microfluidics technology and photo-cross-linking chemistry with a considerable coencapsulation efficiency for Bev and DTX. PVA microgels exhibited sustained drug release at the tumoral acidic conditions as the microgel degradation, and DA moieties on the microgels facilitated Bev with long retention at the tumor tissue, highly blocking the vascular endothelial growth factor (VEGF) and inhibiting tumor angiogenesis, as compared to free Bev or no DA-decorated microgels. In addition, the antitumor activity on the 4T1-Luc breast tumor mouse model treated with Bev/DTX-coloaded microgels showed obviously superior tumor growth inhibition than the other treatment groups, in which the combinational therapy efficacy of Bev and DTX mediated by the tumor-adhesive microgels was further confirmed by the immunohistochemistry (IHC) analysis. These PVA microgels with efficient antiangiogenesis and enhanced cancer chemotherapy provide a highly potential platform to treat different malignant tumors as well as the recurrent and metastatic tumors.

Capping Silica Nanoparticles with Tryptophan-Mediated Cucurbit[8]uril Complex for Targeted Intracellular Drug Delivery Triggered by Tumor-Overexpressed IDO1 Enzyme.

Nanosystems responsive to tumor-specific enzymes are considered as a highly attractive approach to intracellular drug release for targeted cancer therapy. Mesoporous silica nanoparticles are capped with tryptophan-mediated cucurbit[8]uril complex with Fe3 O4 to minimize the premature drug leakage while being able to deliver the payload on demand at the target tissue. The supramolecular interaction between tryptophan and cucurbit[8]uril is disrupted in the presence of indoleamine 2,3-dioxygenase 1 (IDO1) enzyme (abundant in the tumor intracellular microenvironment), which catalyzes the metabolism of tryptophan into N-formylkynurenine, resulting in the disassembly of the "gate-keeper" of the nanocarriers and intracellular release of therapeutics exclusively in tumor cells. The drug release from the nanocarrier with high selectivity to overexpressed IDO1 enzyme induces significant cytotoxicity against HepG2 cells in vitro, as well as the superior antitumor effects in vivo. This robust supramolecular nanosystem with sophisticated structure and property provides a promising platform for intracellular drug release targeting the intrinsic microenvironmental enzyme inside the tumor cells.

Folated pH-degradable nanogels for the simultaneous delivery of docetaxel and an IDO1-inhibitor in enhancing cancer chemo-immunotherapy.

Combining chemotherapy and immunotherapy has been considered as an attractive approach to improve cancer therapy. Here we prepared folated PVA-based nanogels for the simultaneous delivery of docetaxel (DTX) and the indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor NLG919 (N9) for enhancing cancer chemo-immunotherapy. FDA-approved poly(vinyl alcohol) (PVA) with good biocompatibility was modified with vinyl ether acrylate (VEA) groups for UV-crosslinking and acidic degradation. Carboxyl groups were introduced via modification with succinic anhydride for improved drug loading and folic acid (FA) ligands were incorporated for tumor targeting. UV-crosslinked folated PVA nanogels were efficiently taken up by tumor cells followed by endo/lysosomal pH-triggered intracellular drug release, which induced significant cytotoxicity towards 4T1 breast cancer cells in vitro. DTX and N9 co-loaded PVA nanogels exhibited a much higher antitumor efficiency in 4T1 mouse breast cancer models in vivo as compared to the free drug controls. The drug-laden nanogels not only directly killed the tumor cells by DTX, but also induced immunogenic cell death (ICD) promoting intratumoral accumulation of cytotoxic T lymphocytes, and further combining with N9 elevated the intratumoral infiltration of CD8+ T cells and NK cells and inhibited the infiltration of MDSCs, downregulating IDO1-mediated immunosuppression.

Resveratrol attenuates hydrogen peroxide-induced aging through upregulation of autophagy in human umbilical vein endothelial cells.

PURPOSE: Resveratrol (RESV; trans-3,5,4'-trihydroxystilbene) has emerged as a potential new therapeutic for age-related atherosclerotic diseases. However, the effect of RESV on cellular aging and its underlying mechanisms remain unknown. Therefore, the aim of this study was to examine whether RESV can delay cellular aging through upregulation of autophagy. MATERIALS AND METHODS: Human umbilical endothelial vein cells (HUVECs) were divided into four groups: the control group, and the hydrogen peroxide (H2O2) alone, H2O2 + RESV pretreatment, and H2O2 + 3-methyladenine (3-MA) + RESV pretreatment intervention groups. The cell viability was evaluated by a cell counting kit-8 assay. Superoxide dismutase (SOD) activity and intracellular reactive oxygen species (ROS) levels were tested using commercial kits. Senescence-related ß-galactosidase activities were detected by immunohistochemical staining. The expression levels of aging-related and autophagy-related markers, including phosphorylated Rb (p-Rb), LC3, and p62, with or without RESV were measured by Western blotting. RESULTS: Pretreatment with 10 µM RESV increased the cell viability and SOD levels. The remarkably higher positive rate of senescence-associated ß-galactosidase and increased intracellular ROS levels in the H2O2 treatment group were reversed by treatment with 10 µM RESV. As compared to the H2O2 treatment group, 10 µM RESV could upregulate autophagy through the regulation of p-Rb, LC3, and p62 levels. The anti-aging effect of RESV via an autophagy regulation mechanism was further confirmed by the suppression of these effects with 3-MA treatment. CONCLUSION: RESV may reverse and delay the aging process of HUVECs via upregulation of autophagy and could be a candidate therapeutic for age-related atherosclerotic diseases.

Functional Biodegradable Nitric Oxide Donor-Containing Polycarbonate-Based Micelles for Reduction-Triggered Drug Release and Overcoming Multidrug Resistance.

Nitric oxide (NO), as a bioeffector to improve chemosensitivity by reversing multidrug resistance (MDR), is highly attractive for developing combinational delivery systems to deal with MDR tumors, while it is highly challenged by the stability and controlled release of NO during the pathway. Here we design and synthesize a cyclic nitrate trimethylene carbonate monomer (NTC), followed by ring-opening polymerization to prepare amphiphilic biodegradable polycarbonate-based copolymers as polymeric NO donors with tailored contents. The copolymer with desirable molecular weight is readily self-assembled to biodegradable micelles (NO-M) with a uniform size of 130 nm for highly stabilizing NO donors at the physiological conditions, while triggered NO release from micelles is performed at the intracellular reduction conditions. More importantly, NO-M shows superior inhibition of P-gP expression to enhance the chemosensitivity of multidrug-resistant MCF7 cells (MCF7/DOXR). DOX-loaded NO-M (NO-M@DOX) realizes fast DOX release at the intracellular conditions, resulting in more intracellular DOX accumulation and higher antitumor activity mediated by the reduction-triggered NO/DOX release and NO-induced MDR reversal. Furthermore, the in vivo results show that NO-M@DOX effectively suppresses the MCF7/DOXR tumor growth by a combination of directly NO-induced therapy and NO-mediated enhanced chemotherapy; meanwhile, the treatment with NO-M systems have much fewer side effects.

Comparison between 90-degree and 360-degree selective laser trabeculoplasty (SLT): A 2-year follow-up.

PURPOSE: To compare the effect of 90- and 360-degree selective laser trabeculoplasty (SLT) as primary or supplement therapy in patients with glaucoma and ocular hypertension (OHT). METHODS: Patients (>30 years old) with OHT, primary open-angle glaucoma (OAG), pigmentary glaucoma or pseudoexfoliative glaucoma were enrolled in a prospective randomized clinical trial. Patients were sequentially randomized to either 90- or 360-degree SLT. Their intraocular pressure (IOP) was monitored. RESULTS: The survival periods (in days) of the two extents (90 or 360 degrees) of treatment were not statistically significantly different (p = 0.85); only pretreatment IOP level could predict survival of treatment (p = 0.02). CONCLUSION: The 90-degree SLT is as effective as 360-degree SLT. Further studies are warranted to confirm the findings. High baseline IOP could be a factor that predicts treatment success.

Children with mucopolysaccharidosis risk progressive visual dysfunction despite haematopoietic stem cell transplants.

AIM: This prospective study assessed the long-term ocular and visual outcomes of children with mucopolysaccharidoses type I Hurler syndrome (MPS IH) who were treated with haematopoietic stem cell transplants (HSCT). METHODS: Clinical ophthalmological assessments were performed on eight patients at the St Erik Eye Hospital, Huddinge, Stockholm, Sweden, from 2001-2018: The median age at diagnosis and HSCT were 12.2 (range 5.0-16.4) and 16.7 (8.0-20.4) months. The last eye examination was at a median of 13.4 (6.3-19.0) years and follow-up lasted a median of 12.0 (5.0-17.4) years. RESULTS: Poor visual acuity, poor night vision and, or, photophobia were reported by six children. The best corrected visual acuity at the last visit was a median of 0.4 and 0.5 in the right and left eye and had declined significantly in two patients. Corneal opacities had increased despite HSCT in five patients. High hyperopia, at a median of +6 Dioptres, occurred in all patients and stiff corneas in all four patients that were measured. The patients' corrected intraocular pressures were normal. Retinal degeneration was identified in two patients. CONCLUSION: Despite HSCT, the long-term follow-up of patients with MPS IH showed reduced visual acuity due to corneal opacities or retinal degeneration.

Monitoring daily intraocular pressure fluctuations with self-tonometry in healthy subjects.

PURPOSE: To evaluate the accuracy of the intraocular pressure (IOP) measured by healthy subjects with icare® Home and to observe the IOP fluctuation and pattern of IOP fluctuation in healthy subjects over three consecutive days. METHODS: Sixty healthy subjects were recruited to the study. IOP was measured by the subjects themselves and by study staff using icare® Home tonometers on visits 1 and 2, as well as by study staff using Goldmann applanation tonometry (GAT). Furthermore, the subjects measured their IOP at home for three consecutive days. RESULTS: Twenty-three per cent of the study eyes were excluded in the statistical analysis due to dropout or non-compliance to the schedule. Approximately 70% of the icare® Home measurements were within 3 mmHg of the GAT measurements. Ten to 16% of the study eyes had IOP peaks outside office hours. Sixty-three per cent of the study eyes had different IOP patterns on consecutive days. CONCLUSION: Rebound self-tonometry appears to be accurate and could be used to monitor short- and long-term IOP variations. The difference between IOP patterns on consecutive days raises questions as to the certainty of a single IOP measurement as a measure of treatment effect.

Self-tonometry as a complement in the investigation of glaucoma patients.

PURPOSE: To evaluate the reliability of intraocular pressure measured by patients with glaucoma themselves using a new hand-held tonometer and to observe whether the intraocular pressure (IOP) variations have the same pattern on different days while glaucoma treatment is constant. METHODS: Eighty-seven patients diagnosed with open-angle glaucoma or ocular hypertension were recruited to the study. Intraocular pressure measured using Goldmann applanation tonometry (GAT) was compared with IOP measured using tonometry at baseline and on the second visit. Patients measured their IOP at home using the hand-held tonometers. RESULTS: The mean difference between GAT and iCare® values varies from 0 to 1 mmHg. Seventy-eight per cent of iCare® measurements were within 3 mmHg of the GAT measurements. Approximately 64% of the study eyes had higher IOP in the morning than in the afternoon/evening. Circadian patterns differed between consecutive days in 47% of the study eyes. There were IOP peaks outside office hours in up to 16% of the study eyes. CONCLUSION: Measurements made using rebound self-tonometry are accurate and could be used to complement the investigation of patients with glaucoma. Intraocular pressure curves provide valuable data usable when adapting glaucoma treatment.

Measuring corneal hysteresis: threshold estimation of the waveform score from the Ocular Response Analyzer.

BACKGROUND: The aim of this study was to determine a threshold waveform score (WS) for the best score value (BSV) in the Ocular Response Analyzer (ORA). METHODS: Retrospective study. One hundred and thirty-three healthy adults were recruited. Measurements were done with the ORA 2.04. RESULTS: Two hundred and sixty-six eyes were analyzed. Mean age was 56.49 ± 15.97 years. The mean waveform score of the BSV was 7.39 ± 1.32. The waveform scores ranged from 2.8 to 9.7. Kolmogorov-Smirnov test for normality was significant (p ≤ 0.0001). Linear regression showed a significant positive correlation between IOPg (measured with the ORA) and IOP measured with Goldmann applanation tonometry (p ≤ 0.0001), as well as significant negative correlation between the difference IOPg-IOP Goldmann and waveform score of the BSV values. Threshold estimation considering 95 % confidence interval was 7.23. Meanwhile, threshold estimation considering the difference IOPg-IOP Goldmann, for 3 mmHg, was 6.7. CONCLUSIONS: When using the ORA device, we recommend that clinicians try to obtain several waveform score measurements of 7 or above. Waveform scores lower than 7 may render less reliable results.

Corneal hysteresis in mucopolysaccharidosis I and VI.

PURPOSE: High intraocular pressure (IOP) and glaucoma are often suspected in patients with mucopolysaccharidosis (MPS). To determine corneal hysteresis (CH) and IOP in children with mucopolysaccharidosis I-Hurler (MPS I-H) and MPS VI. METHODS: Clinical measurements with ocular response analyzer (ORA). RESULTS: In seven patients, five with MPS I-H treated with stem cell transplantation (SCT), and two with MPS VI, one treated with SCT and the other with enzyme therapy, the IOP was examined with ORA. Ocular response analyzer measurements were made at a median age of 8.7 years in the patients with MPS I-H and at a median age of 9.3 years in the patients with MPS VI. Earlier measurements had raised suspicion of high IOP in one patient. The ORA showed an increased CH and a falsely high IOP values in all 14 eyes. The recalculated IOPs were normal in all 14 eyes. Mild to severe corneal opacities were present in all 14 eyes. Optic disc areas, borders and cupping were clinically normal in the 12 of 14 eyes that were possible to examine. Severe corneal opacities hampered optic disc evaluation in the older patient with MPS VI. Three eyes in two patients had normal thickness of the retinal nerve fibre layer measured with scanning laser polarimetry with corneal compensation (GDx VCC). No patient was diagnosed or treated for glaucoma. CONCLUSION: The IOPs are often falsely high because of an increased resistance of the cornea and correlate to the extent of corneal clouding. In this small, cross-sectional study, it appears that corneal resistance is directly correlated with corneal clouding, although a longitudinal study that evaluates resistance as the cornea clears with treatment would provide more direct evidence that corneal deposits are directly related to resistance. A correct measured IOP can avoid unnecessary medical or surgical hypotensive treatment.