WO2023085447A1 - Method for predicting prognosis of patient having hypertensive anterior uveitis - Google Patents

Abstract

The present invention provides a method for predicting the prognosis of hypertensive anterior uveitis, comprising the steps of: collecting images of the anterior segment of a patient having anterior uveitis through an image collection part; analyzing types of corneal deposits by using the images of the anterior segment; and detecting viruses in the aqueous humor of the patient having anterior uveitis. The cause of anterior uveitis is diagnosed, and a prognosis according to the cause is predicted so that appropriate treatment is provided in parallel, and thus loss of sight caused by complications such as those of glaucoma accompanied by anterior uveitis can be prevented.

Description

A method for predicting the prognosis of patients with ocular hypertension anterior uveitis

This is a technique for predicting the prognosis of patients with ocular hypertension anterior uveitis.

Anterior uveitis (AU) is the most common type of uveitis and occurs in acute, recurrent and chronic forms. Anterior uveitis (AU) has infectious causes such as bacteria, fungi, and viruses, as well as various non-infectious causes such as immune mediators or impostor syndrome. Among the types of anterior uveitis (AU), intraocular pressure anterior uveitis (AU) is associated with mild inflammation of the anterior chamber with elevated intraocular pressure (IOP). Herpes virus is known to be the main cause of ocular hypertension anterior uveitis (AU), and in recent years, herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus have been virus (CMV) has been reported. CMV or rubella virus was recently identified as the cause of hypertensive AU previously diagnosed as Posner-Schlossmann syndrome (PSS) and Fuchs uveitis syndrome (FUS). Although identification of the cause is very important for the treatment of ocular hypertension anterior uveitis, there are few long-term and systematic studies on the spread, cause, clinical progression, and visual outcome of ocular hypertension anterior uveitis (AU).

In addition, if early diagnosis and treatment of ocular hypertension anterior uveitis caused by a virus are not performed, it may progress to glaucoma and cause vision loss.

An object of the present invention is to provide a method for predicting the prognosis of patients with ocular hypertension anterior uveitis.

1. Collecting an anterior segment image of an anterior uveitis patient through an image collection unit; Analyzing the type of corneal deposit through an anterior segment image; And a method for predicting the prognosis of an ocular hypertension anterior uveitis patient comprising detecting a virus in the aqueous humor of an anterior uveitis patient.

2. The method according to 1 above, wherein the virus is one or more selected from the group consisting of herpes simplex virus, varicella-zoster virus, cytomegalovirus and Epstein-Barr virus, and predicting the prognosis of patients with ocular hypertension anterior uveitis.

3. The method for predicting the prognosis of an ocular hypertension anterior uveitis patient according to 1 above, wherein the virus is cytomegalovirus.

4. The method for predicting the prognosis of patients with ocular hypertension anterior uveitis according to 1 above, wherein the method for detecting the virus is to use a multiple polymerase chain reaction.

The present invention provides a method for predicting the prognosis of patients with ocular hypertension anterior uveitis.

The present invention provides a method for predicting the reduction rate and recurrence rate of the number of corneal endothelial cells in a patient by analyzing the type of corneal deposit in the anterior segment of a patient with ocular hypertension anterior uveitis and detecting a virus in the aqueous humor of the patient.

1 shows a representative anterior segment photograph of a patient with corneal deposit (KP). a-c indicate coin-type KPs (white arrows) positive for cytomegalovirus in multiplex PCR. d shows diffuse small-to-medium pigmented KP in herpes simplex virus-positive patients. e represents the KP of the diffuse medium-large lamb fat type of a patient who tested positive for varicella zoster virus in a multiplex PCR test. f shows diffuse corneal edema and multiple microscopic KPs in an Epstein Barr virus-positive patient.

Figure 2 shows the results of multivariate analysis on multipolymerase chain reaction positivity in patients with ocular hypertension anterior uveitis. Positivity by multiplex PCR was only significantly associated with coin type KP (OR = 6.01 [95% CI 1.05-34.51], P = 0.044). PCR stands for polymerase chain reaction, KP for keratoprecipitate, OR for odds ratio, CI for confidence interval, BCVA for best corrected visual acuity, IOP for intraocular pressure, ECC for endothelial cell count, and CCT for central corneal thickness.

Figure 3 shows the results of multivariate analysis on the recurrence of ocular hypertension anterior uveitis patients. Recurrence was significantly associated with PCR positivity (OR = 2.92 [95% CI 1.15-7.41], P = 0.024) and presumptive diagnosis of viral endothelitis (OR = 21.69 [95% CI 1.14-411.53], P = 0.04). .

Figure 4 shows the results of multivariate analysis of Final BCVA (logMAR) in hypertensive anterior uveitis patients. Final BCVA was not significantly associated with low initial BCVA (logMAR) (OR = 2.43 [95% CI 1.05-5.6], P = 0.037) and a presumptive diagnosis of viral endothelitis (OR = 6.3 [95% CI 1.82-21.81], P = 0.004). It was related.

Hereinafter, the present invention will be described in detail.

The present invention relates to a method for predicting the prognosis of patients with ocular hypertension anterior uveitis.

The term “high intraocular pressure anterior uveitis” refers to anterior uveitis involving an intraocular pressure of 25 mmHg or greater.

If viral infectious ocular hypertension anterior uveitis is mistakenly identified as non-infectious ocular hypertension anterior uveitis and only steroid treatment is performed, it may cause steroid glaucoma or viral proliferation, and patients with ocular hypertension anterior uveitis may already have complications of glaucoma. In many cases, the initial treatment period may be missed or vision loss or vision loss may occur due to recurrence. Therefore, by quickly identifying the cause of ocular hypertension anterior uveitis and predicting the resulting prognosis (number of corneal endothelial cells, risk of recurrence) through the method of the present invention, appropriate and rapid treatment can be accompanied.

The present invention comprises the steps of collecting an anterior segment image of an ocular hypertension anterior uveitis patient through an image collection unit; Analyzing the type of corneal deposit through the anterior segment image; And it provides a method for predicting the prognosis of an ocular hypertension anterior uveitis patient comprising the step of detecting a virus in the aqueous humor collected from an ocular hypertension anterior uveitis patient.

The type of corneal deposit can be analyzed through the collected anterior segment images. The types of corneal deposits may be, for example, coin-shaped corneal deposits, mutton-fat corneal deposits, fine corneal deposits, and pigmented corneal deposits (FIG. 1).

The virus to be detected in the aqueous humor of patients with ocular hypertension anterior uveitis may be at least one selected from the group consisting of herpes simplex virus, varicella-zoster virus, cytomegalovirus and Epstein-Barr virus.

A method of detecting the virus in the aqueous humor of patients with ocular hypertension anterior uveitis may be to perform multiplex PCR, but is not limited thereto.

The terms "multiplex polymerase chain reaction", "multiplex PCR", "multiplex polymerase chain reaction" and "multiplex PCR" can be used interchangeably, and multiplex primer pairs are used simultaneously to target multiple target genes in the same reaction. It means a method of amplification in liquid.

By performing multiple polymerase chain reaction, it is possible to check at once whether or not to be infected with herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus, and quickly know which virus caused ocular hypertension anterior uveitis.

In performing the multiplex PCR to detect viruses in the present invention, the sample concentration, the concentration of dNTP, and a suitable temperature are not particularly limited, and the reaction is performed at a sample concentration, dNTP concentration and suitable temperature, etc. that are obvious to those skilled in the art. can be performed. For example, in performing a polypolymerase chain reaction, initial denaturation at 92 ° C to 96 ° C for 10 to 20 minutes or 10 to 15 minutes, denaturation at 92 ° C to 96 ° C for 30 seconds, 58 One cycle may be constituted by annealing at 68° C. to 68° C. for 60 seconds to 120 seconds and extension at 68° C. to 76° C. for 10 seconds to 50 seconds, and repeating the cycle two or more times. Finally, final extension may be performed at 68° C. to 76° C. for 5 to 15 minutes.

The initial corneal endothelial cell count of patients in whom at least one virus selected from the group consisting of herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus was detected in the aqueous humor of patients with ocular hypertension anterior uveitis was not detected. As ocular hypertension anterior uveitis progresses, the number of corneal endothelial cells in patients with detected virus may decrease more rapidly. For example, the initial corneal endothelial cell number of a patient in which the virus is detected is 1900.0/mm ³ or less, and the reduction rate of the corneal endothelial cell number is 25% or more.

In one embodiment of the present invention, early corneal endothelial cells are detected according to whether herpes simplex virus, varicella-zoster virus, cytomegalovirus or Epstein-Barr virus is detected through polypolymerase chain reaction (polypolymerase chain reaction positive) The numbers were different, and the number of initial corneal endothelial cells in patients with virus was significantly lower than the number of endothelial cells in patients without virus (initial number of endothelial cells: 1796.5/mm ³ vs 2146.5/mm ³ , P= 0.011), and the final corneal endothelial cell count after treatment was also significantly lower in patients in whom the virus was detected (1282.0/mm ³ vs 2033.0/mm ³ ; P = 0.04) (Table 5). The reduction in the number of endothelial cells in the cornea of patients with the virus was about 29%, and the reduction in the number of endothelial cells in the patients in which the virus was not detected was about 5%.

In addition, the recurrence rate when one or more viruses selected from the group consisting of herpes simplex virus, varicella-zoster virus, cytomegalovirus, and Epstein-Barr virus is detected in the aqueous humor of patients with ocular hypertension anterior uveitis is The recurrence rate is high compared to , and the probability of recurrence more than 4 times is significantly high. For example, the recurrence rate when a virus is detected is 70% or more, and the recurrence rate 4 or more times is 20% or more.

In one embodiment of the present invention, the recurrence rate is different depending on whether herpes simplex virus, varicella-zoster virus, cytomegalovirus or Epstein-Barr virus is detected through polypolymerase chain reaction (polypolymerase chain reaction positive) , and the recurrence rate of patients in which the virus was detected was higher (about 71.4% of patients in whom the virus was detected had recurrence of ocular hypertension anterior uveitis (20 out of 28 eyes), and about 21.4% (6 out of 28 eyes) About 38.3% of patients in whom no virus was detected had recurrences of ocular hypertension anterior uveitis (23 out of 60 eyes), and about 3.3% (2 out of 60 eyes) had 4 or more relapses (Table 1). 4).

Therefore, by analyzing the type of corneal deposits through anterior segment images of patients with ocular hypertension and confirming whether viruses were detected in the aqueous humor of patients, the number of endothelial cells in the initial stage, their reduction rate, and the possibility of recurrence of ocular hypertension were predicted. can

Hereinafter, the present invention will be described in more detail through examples.

Example

1. Method

1.1. patient

In this study, we retrospectively analyzed the medical records of patients with ocular hypertension anterior uveitis who visited the Ophthalmology Department of Jinju Gyeongsang National University Hospital from January 2015 to December 2019, and 88 patients (88 eyes) with ocular hypertension anterior uveitis was targeted. All patients provided written informed consent and the protocol of this study was approved by the Medical Research Ethics Review Board of Gyeongsang National University Hospital (GNUHIRB-201711019). All procedures followed the principles of the Declaration of Helsinki. Multiplex PCR was performed using an anterior puncture to collect the aqueous humor during a hospital visit. Patients with intraocular pressure greater than 25 mmHg and anterior uveitis were diagnosed as ocular hypertension anterior uveitis, and patients with a history of steroid-induced ocular hypertension were excluded. Immunocompromised patients (i.e., patients diagnosed with acquired immunodeficiency syndrome, patients with known hematological malignancies, or patients requiring immunosuppressive drugs for more than 1 month) and patients with retinal inflammation were also excluded. The presumptive diagnosis was classified into viral endothelitis, FUS-like anterior uveitis, and granulomatous anterior uveitis according to the phenotype of the clinical features of prepuncture anterior uveitis based on the "Phenotypes of viral AU" previously reported by Chan and Chee in 2019. .

All patients underwent slit-lamp biomicroscopy, automated and/or manual refraction, central corneal thickness (CCT), endothelial cell count (ECC), tonometry (using Goldmann applanation tonometry), and dilated fundus examination. . A Pentacam (Oculus Inc., Dutenhofen, Japan) was used for the CCT test, and a Topcon SP2000P reflector microscope (Topcon, Tokyo, Japan) and a CellChek XL reflector microscope (Konan, Irvine, CA, USA) were used for the ECC test. Goldmann applanation tonometry was used.

A comprehensive survey of systemic or ocular history was performed for all patients. First, patients who received systemic (oral or intravenous) antiviral or steroid therapy were excluded from the patient's medical history, whereas patients who received topical antiviral or steroid therapy were included in the patient's medical history. Second, if uveitis was suspected due to drug side effects, especially anti-glaucoma drugs (prostaglandin analogues or brimonidine), they were excluded from the medical history. To evaluate the cause of anterior uveitis, all patients should undergo routine blood tests, including erythrocyte sedimentation rate measurement, C-reactive protein test, syphilis, toxoplasma, tuberculosis and human immunodeficiency virus serology, chest X-ray, and urine analysis. A diagnostic test was performed. In addition, the presence of systemic diseases was examined by confirming fluorescent antinuclear antibody test, human leukocyte antigen-B27, angiotensin converting enzyme, c-antineutrophil cytoplasmic antibody (ANCA), and p-ANCA. Patients with positive factors associated with systemic disease in this test were excluded from this study. To grade the severity of glaucoma, early glaucoma was defined as -5.00 dB or more (mean deviation MD), intermediate glaucoma was defined as -5.01 to -12.00 dB (mean deviation MD), and late glaucoma was defined as visual impairment corresponding to -12.00 dB or less. .

1.2. Anterior chamber paracentesis

All patients underwent anterior puncture under aseptic conditions with local anesthesia in the supine position. After washing with 5% povidone and balanced salt solution, 0.15 mL of aqueous humor was collected using a 30G needle of an insulin syringe through the clear cornea near the limbus. After sampling, it was confirmed that there was no leakage from the aqueous humor, and the ophthalmic moxifloxacin (Moroxacin, Hanmi Pharmaceutical, Seoul, Korea) was applied. No complications (ie, hemorrhage, endophthalmitis or cataract) were observed in 88 patients who underwent anterior puncture.

1.3. Multiplex PCR

Multiplex PCR was performed as previously reported. To detect viral infection in the aqueous humor, Seeplex Meningitis-V1 ACE Detection kit (v2.0; Seegene, Seoul, Korea), which can detect HSV1, HSV2, VZV, EBV, CMV, and HHV6, was used, and the result was nucleic acid extraction , PCR and analysis were derived through three steps. After puncture, DNA was extracted from the sample using the ExiPrepViral DNA/RNA kit according to the protocol recommended by the manufacturer (Bioneer, Seoul, Korea). The extracted nucleic acid (5 μL) was mixed with the reagents of the Seeplex Meningitis-V1 ACE Detection kit (10 × MV1 ACE PM 2 μL, 8-MOP solution 3 μL, 2 × multiplex master mix 10 μL), and PCR was performed using Veriti 96 according to the manufacturer's instructions. -well thermal cycler (Applied Biosystems, Waltham, Mass.). PCR was performed under the following conditions. (1) predenaturation at 94°C for 15 min, (2) denaturation at 94°C for 30 sec, (3) annealing at 63°C for 90 sec, (4) 40 cycle extension at 72°C for 90 sec, (5) Additional extension at 72°C for 10 min. Identical dose amplification products were analyzed using 2% agarose gel electrophoresis with 0.5 mg/mL ethidium bromide staining.

1.4. therapy

First of all, when the patient first visits the hospital, after obtaining aqueous humor for PCR test through puncture, topical levofloxacin (Cravit, Santen Pharmaceutical Co., Ltd., Osaka, Japan) and corticosteroid (Fumelon, Hanlim Pharm. Co. Ltd, Seoul, Korea) was administered 6 times a day. After obtaining the PCR results, the treatment regimen was modified according to the results. The treatment regimen for CMV-positive patients was oral valganciclovir (Valcyte, Roche, Basel, Switzerland) 900 mg twice daily for 6 weeks followed by 450 mg twice daily for 6 weeks. In addition, 2% topical ganciclovir eye drops using intravenous ganciclovir (Cymevene, Roche, Basel, Switzerland) were administered 6 times a day for patients with CMV-positive anterior uveitis during the first month, followed by 2-3 It was administered 4 times a day for 6 months, then gradually reduced to 2-3 times a day for up to 6 months. Patients who tested positive for HSV1, VZV, or EBV ocular hypertension anterior uveitis received oral acyclovir 800 mg three times a day for 4–6 weeks followed by 400–800 mg daily for 4 months. In addition, topical acyclovir ointment (Herpesid, Samil Co. Ltd., Seoul, South Korea) was administered 4 times a day for 6 weeks and then reduced to 2-3 times a day for up to 4 months. In all patients with positive PCR results, the treatment period was more than 6 months, and topical corticosteroids and IOP-lowering drugs were added according to the degree of inflammation and IOP value. For patients with negative PCR results, topical steroids were mainly used, and oral steroids (mg/kg) were used if there was no response to treatment, and the dose was slowly reduced. If there is no response to steroid treatment, oral acyclovir 400 mg/day 3 times (for 6 to 8 weeks) and topical acyclovir ointment 4 times a day for 6 weeks are administered, and the dose is gradually reduced to 2 to 3 times/day for up to 4 months. .

1.5. statistical analysis

Continuous variables are presented as means (± standard deviation, SD) and interquartile ranges, and categorical variables as numbers (percentage). Continuous variables between PCR positive and negative groups were compared using the Mann-Whitney U test, and differences in categorical variables were evaluated using Fisher's exact test. For multivariate analysis, logistic analysis was performed to obtain the risk odds ratio (95% confidence interval; CI) of PCR positivity, recurrence, and final best corrected visual acuity (BCVA). A P-value <0.05 was considered statistically significant. Statistical analysis was performed using R software version 2.2.1 (R Project for Statistical Computing, Vienna, Austria).

2. Results

2.1. Demographic and Clinical Characteristics

Detailed demographic and clinical characteristics of the included patients are shown in Tables 1 and 2. The mean follow-up period of the patients was 33.5 months. The mean age of the patients was 61.0 ± 14.3 years, and 66 patients (75%) were male. There was no difference in these characteristics between the PCR positive and negative groups. Fifty patients (66.8%) were diagnosed with glaucoma or hyperocular hypertension and took one or more antiglaucoma drugs, and 86.4% and 51.1% of patients received steroid and antiviral treatment, respectively, before visiting the hospital. There was no difference in drug use before hospital visit between the PCR-positive and negative groups. There was a statistically significant difference between PCR-positive and negative groups according to presumptive diagnosis (P = 0.042) (Table 1). Table 1 shows the demographic characteristics of patients with ocular hypertension anterior uveitis. (AU = anterior uveitis, FUS = Fuchs uveitis syndrome, IQR = interquartile range, PCR = polymerase chain reaction, SD = standard deviation). *P-values were calculated between PCR negative and positive groups using the Mann-Whitney U test for continuous variables and Fisher's exact test for categorical variables.

Total (N = 88) PCR negative (N = 60) PCR positive (N = 28) P-value* male (%) 66 (75.0%) 43 (71.7%) 23 (82.1%) 0.428 Age of onset (years) (± SD) 61.0 ± 14.3 59.8 ± 14.3 63.5 ± 14.1 0.250 Left and right difference (right, %) 49 (55.7%) 35 (58.3%) 14 (50.0%) 1.000 Interval between symptom onset and first visit (days) (IQR) 20.5 (5-90) 20.5 (5-75) 22.5 (10-90) 0.553 Follow-up period (months) 33.5 (6.0-63.5) 32.0 (6.0-61.5) 38.0 (17.0-63.5) 0.172 Previous glaucoma medication 0.176 0 38 (43.2%) 27 (45.0%) 11 (39.3%) One 17 (19.3%) 12 (20.0%) 5 (17.9%) 2 16 (18.2%) 13 (21.7%) 3 (10.7%) 3 17 (19.3%) 8 (13.3%) 9 (32.1%) Previous treatment before the visit (%) steroid 76 (86.4%) 49 (81.7%) 27 (96.4%) 0.122 antiviral 45 (51.1%) 31 (51.7%) 14 (50.0%) 1.000 Presumed diagnosis (n/%) 0.042 Viral endotheliitis 52 (59.1%) 32 (53.3%) 20 (71.4%) FUS 15 (17.0%) 9 (15.0%) 6 (21.4%) Granulomatous AU 21 (23.9%) 19 (31.7%) 2 (7.1%) Systemic disease (n/%) High blood pressure 29 (33.0%) 21 (35.0%) 8 (28.6%) 0.723 diabetes 23 (26.1%) 16 (26.7%) 7 (25.0%) 1.000 rheumatic disease 3 (3.4%) 2 (3.3%) 1 (3.6%) 1.000

There was no difference in the symptoms of the patients according to the PCR results. Median initial BCVA was 0.4 logMAR and median initial IOP was 22.5 mmHg, showing no significant difference between groups. There was no difference in the initial central corneal thickness (CCT) between the two groups, but the initial endothelial cell count (ECC) was 2146.5/mm ² in the PCR-negative group and 1796.5/mm ² in the PCR-positive group, showing a significant (P = 0.011) difference. Looking at the clinical characteristics of the anterior segment, there was a significant difference in the type and size of pigmented corneal deposits (KP) between the PCR positive and negative groups (P = 0.011) (FIG. 1). However, corneal edema, anterior chamber reaction, and iris involvement were not different between the two groups. As a result of analyzing the severity of glaucoma in the enrolled patients, 45.5% had intermediate glaucoma (average deviation of -5.01 to -12.00 dB in the 30-2 visual field test) or more severe, and there was no significant difference between the groups (Table 2). Table 2 shows the clinical characteristics of patients with ocular hypertension anterior uveitis (BCVA (best corrected visual acuity) is the best corrected visual acuity, CCT (central corneal thickness) is the central corneal thickness, ECC (endothelial cell count) is the number of corneal endothelial cells, KP (keratoprecipitate) is the corneal deposit, IOP (intraocular pressure) is the intraocular pressure, IQR (interquartile range) is the interquartile range, MAR (minimum angle of resolution) is the minimum resolution angle, PCR (polymerase chain reaction) is the polymerase chain reaction means). P-values were calculated between the PCR negative and positive groups using the Mann-Whitney U test for continuous variables and Fisher's exact test for categorical variables.

Total (N = 88) PCR negative (N = 60) PCR positive (N = 28) P-value* Symptom type (n/%) eye pain 32 (36.4%) 21 (35.0%) 11 (39.3%) 0.880 congestion 87 (98.9%) 60 (100.0%) 27 (96.4%) 0.695 reduced vision 65 (73.9%) 44 (73.3%) 21 (75.0%) 1.000 Initial BCVA (logMAR) (IQR) 0.4 (0.2-1.0) 0.4 (0.2-0.9) 0.4 (0.2-1.0) 0.888 Initial IOP (mmHg) (IQR) 22.5 (14.0-33.0) 20.5 (14.0-32.0) 26.5 (16.0-33.0) 0.358 Initial ECC (/mm ² ) (IQR) 2000.0 (1462.5-2519.0) 2146.5 (1672.5-2602.0) 1796.5 (1000.0-2154.0) 0.011 Initial CCT (um) (IQR) 556.0 (527.5-614.5) 557.5 (525.0-15.0) 545.0 (530.0-609.5) 1.000 Corneal opacity (n/%) 21 (23.9%) 17 (28.3%) 4 (14.3%) 0.241 KPs (corneal deposits) 0.011 Fine 44 (50.0%) 35 (58.3%) 9 (32.1%) Mutton-Fat 17 (19.3%) 11 (18.3%) 6 (21.4%) Coin-shaped 23 (26.1%) 10 (16.7%) 13 (46.4%) Pigmented 4 (4.5%) 4 (6.7%) 0 (0.0%) Corneal edema 87 (98.9%) 59 (98.3%) 28 (100.0%) 1.000 Anterior chamber inflammation 0.925 Trace ~ + 1 65 (73.9%) 45 (75.0%) 20 (71.4%) > + 1 23 (26.1%) 15 (25.0%) 8 (28.6%) Iris atrophy 0.822 Sectoral 12 (13.6%) 8 (13.3%) 4 (14.3%) Diffuse 10 (11.4%) 6 (10.0%) 4 (14.3%) Lens status 0.948 Pseudophakia 9 (10.2%) 6 (10.0%) 3 (10.7%) Phakia 79 (89.8%) 54 (90.0%) 25 (89.3%) Aphakia 0 (0%) 0 (0%) 0 (0%) Glaucoma (glaucoma progression) 0.988 No 37 (42.0%) 25 (41.7%) 12 (42.9%) Early 11 (12.5%) 8 (13.3%) 3 (10.7%) Moderate 22 (25.0%) 15 (25.0%) 7 (25.0%) Advanced 18 (20.5%) 12 (20.0%) 6 (21.4%)

2.2. Multiple PCR results

A total of 28/88 eyes (31.8%) were PCR positive. Among these 28 eyes, HSV was 6 eyes (6.8%), VZV was 7 eyes (8.0%), CMV was 14 eyes (15.9%), and EBV was 1 eye (1.1%). In comparison between presumptive diagnosis and PCR positivity, PCR was positive in 20 eyes with the presumptive diagnosis of viral endothelitis, 6 eyes with the presumptive diagnosis of FUS, and 2 eyes with the presumptive diagnosis of granulomatous anterior uveitis (Table 3). Table 3 shows multiple PCR results in hypertensive anterior uveitis (AU is anterior uveitis, CMV is cytomegalovirus, EBV is Epstein-Barr virus, FUS is Fuchs uveitis syndrome, HSV is herpes simplex virus, PCR is polymerase chain reaction, VZV is varicella -zoster virus).

Presumptive diagnosis
Total (N = 88)
PCR negative (N = 60) PCR positive (N = 28)
Total HSV VZV CMV EBV Viral endotheliitis 52 32 6 4 10 0 20 FUS 15 9 0 2 3 One 6 Granulomatous AU 21 19 0 One One 0 2

2.3. Clinical course and outcome

There was no significant difference in both topical steroid treatment and systemic steroid treatment between the PCR-positive and negative groups, but there was a significant difference in antiviral treatment between the PCR-positive and negative groups (topical, P = 0.001, systemic, P < 0.001). . The PCR-positive group showed a significantly higher recurrence rate (P=0.04) than the PCR-negative group at 53.6%, and the recurrence frequency also showed a significant difference between the two groups (P=0.017) (Table 4). Table 4 shows during-treatment management and relapse numbers of patients with ocular hypertension anterior uveitis.

Total (N = 88) PCR negative (N = 60) PCR positive (N = 28) P -value* therapy topical steroids 87 (98.9%) 59 (98.3%) 28 (100.0%) 1.000 systemic steroids 35 (39.8%) 25 (41.7%) 10 (35.7%) 0.766 topical antiviral 0.001 Acyclovir 37 (42.0%) 24 (40.0%) 13 (46.4%) Ganciclovir 31 (35.2%) 16 (26.7%) 15 (53.6%) systemic antivirals <0.001 Acyclovir 45 (51.1%) 31 (51.7%) 14 (50.0%) Ganciclovir 11 (12.5%) 1 (1.7%) 10 (35.7%) Recurrence (n/%) 32 (36.4%) 17 (28.3%) 15 (53.6%) 0.040 recurrence frequency 0.017 One 11 (12.5%) 6 (10.0%) 5 (17.9%) 2-3 17 (19.3%) 15 (25.0%) 9 (32.2%) > 3 8 (9%) 2 (3.3%) 6 (21.4%)

There were no significant differences in best-corrected visual acuity (BCVA), intraocular pressure (IOP), and CCT between the groups, but in the PCR-positive group, initial ECC (1796.5/mm3 vs 2146.5/mm3, P=0.011) and final ECC (1796.5/mm3 vs 2033.0 /mm3; P = 0.04) was significantly lower than the PCR negative group (Table 5). Table 5 shows the comparison of BCVA, IOP, ECC and CCT between PCR negative and PCR positive groups in ocular hypertension anterior uveitis (BCVA is best corrected visual acuity, CCT is central corneal thickness, ECC is endothelial cell count, IOP is intraocular pressure, IQR stands for interquartile range, MAR stands for minimum angle of resolution, and PCR stands for polymerase chain reaction).

Total (N = 88) PCR negative (N = 60) PCR positive (N = 28) P-value* BCVA (logMAR) (IQR) Initial 0.4 (0.2-1.0) 0.4 (0.2-0.9) 0.4 (0.2-1.0) 0.888 Final 0.2 (0.0- 0.7) 0.2 (0.0-0.8) 0.2 (0.0-0.6) 0.571 IOP (mmHg) (IQR) Initial 22.5 (15.0-32.0) 20.5 (14.0-32.0) 26.5 (16.0-33.0) 0.358 Final 14.0 (12.0-17.0) 14.0 (11.5-16.0) 15.5 (12.0-17.0) 0.562 ECC (/mm ² ) (IQR) Initial 2000.0 (1462.5-2519.0) 2146.5 (1672.5-2602.0) 1796.5 (1000.0-2154.0) 0.011 Final 1766.5 (936.0-2448.0) 2033.0 (1424.0-2490.5) 1282.0 (730.5-2361.5) 0.040 Unaffected eye 2536.5 (2224.5-2809.0) 2552.0 (2296.5-2871.0) 2366.0 (2195.5-2758.5) 0.241 CCT (μm) (IQR) Initial 556.0 (527.5-614.5) 557.5 (525.0-615.0) 545.0 (530.0-609.5) 1.000 Final 534.4 (481.6-587.2) 537.0 (482.9-591.1) 528.9 (478.6-579.2) 0.506 Unaffected eye 530.0 (510.0-554.0) 530.0 (510.0-553.0) 531.0 (509.5-554.0) 0.791

There was no difference between the groups in complications and complications of surgery. Of the 88 patients, 3 (3.4%) progressed to bullous keratopathy and 1 patient (1.1%) underwent a full-thickness keratoplasty (Table 6). Table 6 is a table of complications and complications of surgery in patients with ocular hypertension anterior uveitis (PCR stands for polymerase chain reaction and PKP stands for penetrating keratoplasty).

Total (N = 88) PCR negative (N = 60) PCR positive (N = 28) P-value* Complications 0.265 Cataract 18 (20.5%) 10 (16.7%) 8 (28.6%) Glaucoma 39 (44.3%) 25 (41.7%) 14 (50.0%) Corneal perforation 2 (2.3%) 1 (1.7%) 1 (3.6%) Bullous keratopathy 3 (3.4%) 3 (5.0%) 0 (0.0%) Surgery for complications 0.640 Cataract surgery 13 (14.8%) 7 (11.7%) 6 (21.4%) Glaucoma surgery 24 (27.3%) 16 (26.7%) 8 (28.6%) Corneal surgery 2 (2.3%) 1 (1.7%) 1 (3.6%) PKP (Phole Layer Keratoplasty) 1 (1.1%) 1 (1.7%) 0 (0.0%)

2.4. Risk factors for PCR positivity, relapse and definitive BCVA.

Multivariate regression analysis was performed for PCR positivity, relapse and final BCVA (see Supplementary Tables S1, S2 and S3). A higher PCR-positive rate was only observed in patients with coin-type KP among several variables (OR = 6.01 [95% CI 1.05-34.51], P = 0.044) (Figure 1). Recurrence was significant in the PCR-positive group (OR = 2.92 [95% CI 1.15-7.41], P = 0.024) and in patients with a presumptive diagnosis of viral endothelitis (OR = 21.69 [95% CI 1.14-411.53], P = 0.04). occurred more frequently. (Fig. 2). Lower final BCVA was significantly associated with lower initial BCVA (OR = 2.43 [95% CI 1.05–5.6], P = 0.037) and presumptive diagnosis of viral endothelitis (OR = 6.3 [95% CI 1.82–21.81], P = 0.004). was associated (Fig. 3).

Claims (4)

Collecting an anterior segment image of an anterior uveitis patient through an image collection unit; Analyzing the type of corneal deposit through the anterior segment image; and A method for predicting the prognosis of an ocular hypertension anterior uveitis patient comprising the step of detecting a virus in the aqueous humor of the anterior uveitis patient. The method according to claim 1, wherein the virus is one or more selected from the group consisting of herpes simplex virus, varicella-zoster virus, cytomegalovirus and Epstein-Barr virus, the method for predicting the prognosis of patients with ocular hypertension anterior uveitis. The method for predicting the prognosis of patients with ocular hypertension anterior uveitis according to claim 1, wherein the virus is cytomegalovirus. The method according to claim 1, wherein the method for detecting the virus is to use a multiple polymerase chain reaction, the method for predicting the prognosis of patients with ocular hypertension anterior uveitis.

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