JPH02232030A - Ophthalmology diagnostic method - Google Patents

Ophthalmology diagnostic method

Info

Publication number
JPH02232030A
JPH02232030A JP1051956A JP5195689A JPH02232030A JP H02232030 A JPH02232030 A JP H02232030A JP 1051956 A JP1051956 A JP 1051956A JP 5195689 A JP5195689 A JP 5195689A JP H02232030 A JPH02232030 A JP H02232030A
Authority
JP
Japan
Prior art keywords
time
data
signal
value
measurement
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
JP1051956A
Other languages
Japanese (ja)
Inventor
Yoshinaga Aizu
佳永 相津
Koji Ogino
浩二 荻野
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Kowa Co Ltd
Original Assignee
Kowa Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kowa Co Ltd filed Critical Kowa Co Ltd
Priority to JP1051956A priority Critical patent/JPH02232030A/en
Priority to EP90302101A priority patent/EP0389120B1/en
Priority to DE69016071T priority patent/DE69016071T2/en
Priority to US07/489,284 priority patent/US5116116A/en
Publication of JPH02232030A publication Critical patent/JPH02232030A/en
Pending legal-status Critical Current

Links

Abstract

PURPOSE:To obtain an exact correlation data value by counting a photoelectric detection signal as a photoelectric pulse every prescribed unit sampling time, storing a counted value to a memory over one measuring time, successively calculating a photon correlative function and a time correlation length every unit time for stored data after measurement is finished and comparing the time correlation length with a prescribed reference value. CONSTITUTION:A speckle signal counts the time sequential data of the photoelectric pulse corresponding to the intensity of light through a photon counting unit 52 every prescribed time and the data are successively stored to a memory 57. After the measurement is finished, the data are read from the memory 57 and the photon correlative function is calculated by a correlation device 53. Then, the calculated function is displayed and outputted to a CRT 55 or a printer 56 together with an analyzed and evaluated result. Namely, the pulse is counted every prescribed short sampling time DELTAt and the counted values are stored to the memory as n1, n2, n3-ni-nm. The DELTAt is set to a time to be counted while referring to a value taucmin in a measure considered as shortest out of a time correlation length tauc, which is obtained in the signal to be measured, and enough dividing the value.

Description

【発明の詳細な説明】 [産業上の利用分野] 本発明は眼科診断方法,特に眼底に所定径のレーザー光
を照射し、眼底生体組織からの散乱反射光によって観測
面に形成されるレーザースペックルパターンの変動を、
所定径の微小円形検出開口を介してスペックル光強度変
化として検出し、その光子相関関数を求めることにより
眼底組織の血流状態を測定する眼科誇断方法に関するも
のである. [従来の技術] 眼底にレーザー光を照射し、網膜等の組織の血管血流を
測定する方法としては“InvetigativeOp
hthal+mology  .Vo1.ll.No.
ll,p.936.1972年11月. “Scien
ce  ,Vo1.l86.Nov.29.p.830
.1974年をはじめ特開昭55−75668. 55
−75669. 55−75670号公報、特開昭52
−142885号公報(英国13132/76.USP
4.166.695に対応),特開昭56−12503
3号公報(英国(GB]79/37799に対応)、特
開昭58−118730号公報IUsP 4,402.
601に対応)あルイはasp4.142.796など
に示されるレーザードップラー法が知られている.しか
し、ドップラー法は光学系の複雑さ、精密さ、取り扱い
の煩雑さ、測定結果の不安定さ、不確定さなどから、実
用化が困難なのが現状である. これらの問題を解決するために本出願人により、既に皮
膚血流計測などに応用されているレーザースペックル法
(例えば、特開昭60−199430.60−2032
35. 60−203236号公報あるいはOptic
sLetter Vol.10 ,No.3. 198
5年3月. p.104などで示される)を眼領域に対
して適用し、眼組織の血流状態を評価する方法が提案さ
れている.これらは特開昭62−275431号公報(
USP 4.743.l07,EPC2348691,
特開昭63−238843号公報(EPC 28424
8)、特開昭63−242220号公報(EPC 28
5 314)として出願されている. これらの公報に記載された方法では、例えば眼底を測定
する場合、眼底に対する光学的なフーリ工変換面やフラ
ウンホーファ一回折面、または眼底と共役な結像面(あ
るいは拡大結像面)に形成される時間変動スペックルパ
ターンの強度変化を検出開口を用いて抽出するようにし
ている.[発明が解決しようとする課題] この中で特定の1本の血管の血流を評価する場合はスペ
ックルパターンの検出を像面上で行なえば良い.これに
ついて前記出願の特開昭63−242220号公報(E
PC 285314)  に記載されている.この方法
では、拡大した像面上の所望の血管像の上に検出開口を
設定し、そこでの像面スペックルパターンの時間的な強
度変動を抽出してスペックル信号を得るようにしている
.したがって測定中に眼球運動や装置と被検眼の相対的
位置ずれ、アライメントのず′れ、振動など、種々の要
因で検出面上の眼底像が横ずれすれば、測定中の血管像
が検出開口の位置からはずれたり、血管壁にさしかかっ
たり、隣の別の血管が検出位置に入ってしまったりとい
う事態が頻繁に起こる.これは臨床時の疾患眼では特に
固視が不十分であったり,被検者の恐怖心等でたえず生
じる大きな問題である. 従って,1つの測定から得られる信号の相関関数をみる
と種々の成分が混在したものとなり正しい血管血流が毎
回安定に再現性よく測定できなかった.また一度測定し
た相関関数の曲線データから不用な成分を除去し、本来
の血管血流信号を抽出することは非常に困難な作業であ
り、現実的でない.すなわちどんな成分が不用であり、
それがどの程度含まれて最終結果に寄与しているか不明
な為である.また測定中にまばたきや瞬間的なノイズ不
用信号が入った場合、測定した相関データの形がくずれ
たりして,この場合も正し《評価ができなくなり、単な
る瞬間の信号のために1測定が無駄となり再度とり直し
をしなければならなかった. 従って、本発明はこのような問題点を解決するためにな
されたもので、確実な相関データ値を得、正確な眼科診
断が可能な眼科診断方法を提供することを課題とする. r課題を解決するための十段J このような課題を解決するために、本発明では、眼底に
所定径のレーザー光を照射し、眼底生体組織からの散乱
反射光によって観測面に形成されるレーザースペックル
パターンの変動を、検出開口を介してスペックル光強度
変化として光電検出し、その光子相関関数を測定した結
果に基づいて、眼底組織の血流状態を測定する眼科診断
方法において、光電検出信号を所定の単位サンプリング
時間ごとに光電子パルスとして計数し、その計数値デー
タな一測定時間内にわたって時系列的にコンピュータの
メモリに格納し,測定終了後格納されたデータを複数の
ユニット時間毎に分割して各ユニット時間ごとに順次光
子相関関数と時間相関長?:Cを求め,前記時間相関長
を所定の基準値と比較することにより測定データを分類
する構成を採用した. [作用] 本発明実施例では、眼底からの微弱光スペックルを光電
子パルス信号として検出,その時系列パルスを所定のサ
ンプリング時間毎に計数した値をメモリに格納しておき
、測定終了後、再度データを読み出して評価し,あらか
じめ設定していた基準を基に、血管からの信号か周辺組
織にはずれた時の信号か、どちらとも言えない不明確な
信号か等の判別を行ないグループ分けし、個々について
最終評価をするようにした. これにより、異なった信号成分を混在せず個別に評価で
き、眼底が動いてしまった時でも、血管からの信号のみ
を抽出できるので正しい評価ができ、データも無駄にな
らず有効に使える.この判別により,周辺組織に存在す
る毛細血管領域の血流状態や脈絡膜層の血流状態も評価
できる可能性があり,非常に有効な方法となる. [実施例] 以下、図面に示す実施例に従い本発明を詳細に説明する
.本発明は眼領域の特に眼底を対象としており,以下で
は眼底カメラを使用して眼底血流を測定する場合を例に
して説明する. 第1図は、本発明に係る方法が適用される装置全体の概
略図である.例えば、赤色のHe−Ne(波長632.
 8n■)レーザー光源Iからのレーザー光束は、コン
デンサレンズ1′を介し光強度を調整するための光量調
整フィルター2を通過する.さらに、リレーレンズ3、
4を介して眼底カメラの眼底照明光学系に導かれる. またリレーレンズ3と4の間には絞り5と6が設置され
ており、これによって眼底に8けるレーザー光の照射領
域の大きさと形状を選択するようになっている.また,
レーザー光源lの出射口にはシャッター7があり、必要
に応じて開閉する.リレーレンズ4で導かれたレーザー
光は第2図に示すように眼底照明光学系内のリングスリ
ット8の環状開口8aの一部に設置したミラー9で反射
されて、眼底観察撮影用光束が眼底に入射するのと同じ
光路上に導かれる.このため、レーザー光はリレーレン
ズ10、l1を介して穴開きミラーI2で反射され、対
物レンズ13′を介して被検眼13の角膜13aの上に
一度集光した後、拡散する状態で眼底13bに達して、
血管径に比べて広い照射領域を形成する. この照射領域は、眼底カメラとして用いられる照明光学
系によって照明され、観察が容易にされる。この観察光
学系は、撮影光源24と同一光軸上に配置された観察光
源22、コンデンサレンズ23、コンデンサレンズ25
.フィルター27、ミラー26から構成される.レーザ
ー光はこの観察撮影光束と同じ光路に配置されるため、
眼底カメラの左右、上下のスウイング機構や固視誘導機
構を利用してレーザー光を眼底の13bの所望の位置に
照射することができる. なお、コンデンサレンズ25とミラー26間に配置され
るフィルター27は、第3図に図示したように波長分離
フィルターとして構成されるので,観察、損影光に含ま
れる赤色成分はカットされる. レーザー光が眼底血管内を移動する血球で散乱されて生
ずるスペックル光は、再び対物レンズ13′で受光され
、穴開きミラーl2を通過して機影レンズ14ならびに
波長分離ミラーl5に到達する.この波長分離ミラー1
5は、フィルター27と同様第3図に図示したような分
光特性を有しており,赤色域の波長の光の大部分が反射
され,それ以外の光は透過するので、He−Neレーザ
ー光によって生じたスペックル光(赤色)は、大部分が
反射される.この反射光はレンズ16で一度、像面35
に結像されさらに顕微鏡光学系l9の対物レンズ19a
と接眼レンズ19bを介して拡大される.拡大像は検出
開口20を通過し、再び集光レンズ2lで集められ、光
電子増倍管(フォトマル)40で検出される.光電子増
倍管40の前にはシャッター40′が配置され、開放時
に得られるそこからの出力信号は信号処理回路50に入
力される. この信号処理回路50は第4図に示すようにアンブ51
、光子計数ユニット52、相関器53、マイクロコンピ
ュータ54、CRT55、プリンタ56、メモリ57か
ら構成される. 一方,波長分離ミラーl5を通過した光は,リレーレン
ズ28、跳ね上げミラー29,ミラー30、レチクル3
l、接眼レンズ33を介して観察でき、また撮影フィル
ム32で撮影できるように構成されている. このように構成された装置において、まず電源をオンに
した後被検者を設定し、観察光学系22〜26を介し被
検眼l3の眼底13bを観察し、レーザー光源lを作動
する.この時光量調整フィルター2で出力レベルを調整
時のレベルにし、絞り5,6でレーザー照射領域の大き
さ,形状を設定し、シャッター7を開放し,測定位置を
設定してから観察光学系28〜31を介してスペックル
パターンを確認する. 本実施例においては、レーザー
照射を容易にするために、眼底13bの測定部位でのレ
ーザー光照射領域を血管に比べて広い領域,例えば1〜
3msφのように設定するため、この中には、毛細血管
の他に、比較的太い血管が複数本含まれる場合も当然あ
ろうる.したがって特定の1本の血管の血流を測定する
ために,拡大像面上にて測定すべき血管像を選択し,そ
の像中に検出開口20を設定する.すなわち眼底の共役
像を第1図の結像面35に形成する.これを顕微鏡光学
系19の対物レンズ19aと接眼レンズ19bで拡大し
,その拡大像の面に検出開口20を置いてスペックル光
強度変化を検出する.検出された光は集光レンズ2lで
集められ、光電子増倍管40で信号に変換される(シャ
ッタ40′は開放されている).測定時光電子増倍管4
0からの出力は,血球の移動に伴い時間と共に変動する
スペックル信号となる.スペックル信号は信号処理回路
50内のアンブ5lで増幅され、光子計数ユニット52
を介して光強度に応じた光電子パルスの時系列データを
一定の時間毎に計数し、その計数値を紅メモリ57に格
納する.?M定後メモリ57からデータを読みだし相閏
器53で光子相閏閏数を求め,解析、評価結果とあわせ
てCRT55あるいはプリンタ56に表示出力される.
これらの一連の制御はマイクロコンピュータ54で行わ
れる.上述したように本実施例では、検出開口20は拡
大像面に置かれるので、レーザー照射領域中の所望の測
定しようとする血管像を選択し,その血管像内に検出開
口20が設置されるように検出開口20の位置あるいは
対象眼l3の固視を調整することで、特定の1本の血管
血流を測定することができる. 検出開口20としては、ビンホールなどの微小円形開口
が良好に使える.例えば,第5図のように所望の血管1
本60が拡大像で得られている時,少な《とも、この像
上での血管径よりは小さい径を持つ第6図のようなピン
ホール6lを血管内の像面スペックル62が変動してい
る部分に配置してやれば検出開口20をスペックルが横
切るのに応じて、検出光強度が変化しスペックル信号が
得られる. 実際に観測される像面スペックル62は、多重散乱効果
などにより,生体からのスペックル特有のボイリング的
な運動をする.つまり、血球が一定方向に流れて移動し
ていても、像面スペックル62は単純な像のように流れ
に応じて一定方向に移動する、いわゆる並進運動になる
のではなく個々のスペックルが、場所を変えず、その場
その場で時間と共にランダムに明暗の点滅を繰り返し,
全体として斑点模様のスペックルパターンが絶えず、ラ
ンダムに強度変動を起こすような性質の運動であること
が分かってきた.しかし,この場合にもビンホール6l
でのスペックルの点滅の不規則変化がスペックル信号と
なって得られることにはまったく変りはない. 血流が速ければ、像面スペックル62が拡大像上で明暗
の点滅を繰り返す変動の速度も速くなり、スペックル信
号の時間変化が速《なるため、信号は高周波成分が多く
なる.これを、信号処理回路50で信号の自己相関関数
を求め、その相関時間によって減衰度,を評価する.そ
の場合は例えば第7図のように相関値がl/e(または
l/2など)になる遅れ時間を相関時間−ccとすれば
、その逆数l/てCと像面スペックル62の変動速度が
直線関係にある.像面スペックル62の変動速度は血流
速度を直接反映しているので,1/τCより血流速度V
が第8図のような関係から評価できる. 信号処理回路50内では光子計数ユニット52から得ら
れる時系列パルス信号は、第9図(b)のように(a)
のスペックル信号の強度に比例した密度でパルス列信号
に変換される.これを1つ1つメモリに格納するのは非
常に多大なメモリを要し、かつ高速の時間応答性が処理
系に要求され実用的でない. 従って・、本実施例では、所定の短いサンプリング時間
Δtごとに、第9図(C)のごとくパルスを計数し、そ
の計数値をnl.n2.n3.=−ni・−n mとし
てメモリに格納する.従って、1つの測定時間T中にm
回のサンプリングが行なわれ,m個のデータが格納され
る.すなわちT=mΔtとなる.Δtは測定しようとす
る信号が有する時間相関長てCのうち最短と思われる程
度の値τcminを参考に,それを十分に分割して測定
できる時間に設定するのがよい.例えばτcmin=2
 0 71 secであれば、Δt≦0.5 〜1 u
secの値に設定する.というのはΔtが最小時間単位
となって測定の時間分解能を決めるからである.次に第
10図(a).(b)に示すように、1つの測定時間T
=mΔtでm個のデータを格納した時、T f!:m 
/ h個に等分割し、各分割時間T′=hΔtをユニッ
ト時間Ul.U2.U3=Uw/hとし、第IO図(C
)のように各ユニット毎に順次相関関数を求めていく.
この時U1からUs/hまで同一の遅れ時間Δτを設定
しても良いし,個々に最適なΔτを設定しても良い.こ
うしてI澗定T内をm/h個に分けた時間分解能T’=
hΔtで1つの測定が時分割評価できるようになる. 但しT”=hΔtが短かすぎると各ユニットの相関関数
が十分に収束しないので、Δt<<T”が必要である.
また分割数が少な<T’がTに近いと、時間分割の意味
がないので、少なくともT ’ <T/10 (m/h
21 0)の条件が好ましい.この時分解数m/hは何
度でも繰り返して変更できるし、最適分解数を探すこと
もできる.途中,まばたき等で明らかに異常なデータが
あれば、それを含むユニットは除いて評価することもで
きるので臨床上大いに実用的である.各ユニットの相関
関数が第!O図(C)のように得られたら,各々スムー
ジング後に相関時間t Cl.  1: C2. r.
 c3− z cm/hを求める.一般に像面検出の場
合,血管からの信号の場合、第11図のようにスペック
ルの動きが速く、τCは短くなり、周辺組織からの信号
の場合第12図のようにスペックルの動きは遅く,τC
は長くなる.血管信号でのてCのしきい値をてV、周辺
組織信号でのてCのしきい値をてtとしてあらかじめ設
定しておく. これらのデータは複数の人眼データから統計的に調べて
大略の値が得られている.また必要に応じて設定値τV
.てtは変更可能である.そこで各ユニウトのτC(て
cl. てc2・・−τC■/h)を順次τV,てtで
判別してグループ分けを行なう.すなわち(i)τC〈
τv . (iilτV≦てC≦τt. (iiil 
てt〈てCの3つに分割する.区分けした後にグループ
毎にτCの平均値を算出すれば、(i)の平均iciは
血管信号の値、(ii)の平均テ丁はどちらとも言えな
い不確定なデータの値、(iii)の平均てciiiが
周辺組織信号の値と分けて評価できたことになる. このように測定中に測定点が血管からはずれても、また
偶然にも再び血管に戻ったような場合にも血管部を測定
していた時のデータのみを集めてきて評価しており、測
定結果が良好に評価できると共に無駄にならず,効率の
良い臨床計測が可能となる.また血管壁付近のデータ等
は(ii)のグループに分けられるため、血管壁付近の
遅い血管血脈の測定データを(i)のグループで評価す
ることは避けられる. また逆にそうした成分も含めて(i)としてオーバー才
一ルに評価したいのであれば、しきい値τVを長めに調
整すればよい.測定データのうちまばたきやノイズ等で
明らかに異常なデータも上記グループ分けで少なくとも
(i)に混入することはなく、除いて評価できるため大
変実用的である.この時(iii)のデータは毛細血管
領域や脈絡膜の血流状態の評価に使える可能性があり,
全体として無駄になるデータは殆どなく、動きがあって
も評価が可能なため,再測定は必要なくなる.また第1
3図で各グループごとのT.Cの平均値を出すかわりに
、振り分けられたτCのユニットの番号(Ulなら1番
目、Uiならi番目)をもとに、(il に属するユニ
ット中のnの全データをつなぎあわせて1つの相関関数
を演算し、スムージングしてτciを求めてもよい. 
(ii)や(iii)についても同様な処理を行いてc
ii . τciiiを求める. さらに第13図で得た各ユニット毎のT Cl.てc2
−・・の逆数を第14図のように時間軸スケールに対し
てプロットし、しきい値l/てV.1/τtを併せてラ
イン表示させl/てc>1/τV11/ を血管信号、l / τV 21 / t c > 1
 / T: tを不確定信号、l/τt≧l/τcを周
辺組織信号として表示することによって、例えば第14
図のよτ゜ うな特性図を得ることが出きる.同図の例について言え
ば、途中で血管からはずれて再び戻ったことが推察でき
る.したがって測定データの示す時系列的な変化の様子
が良くわかり、評価の上で大いに役立つ. また第14図中のあるデータ75は血管信号となってい
るが、これがもしデータ75′のようなブロツットで周
辺組織信号になった場合、これはデータ75 (75”
)の前後間近のデータがl/τC,≧1 7 t: v
であることから、ユニットU2のみ血管から、はずれて
いたとは考^にく《、これはまばたきや他の不用なノイ
ズにより正しい測定ができなかったという評価を加える
ことができる.すなわちデータの時系列変化が系統的で
あるか否かを第14図から判定、考察できる点も非常に
有用である. また上記の例の特別なケースとして、ZV=ztとし.
rc<zv=itとzc>T.v=τtの2グループに
分けて評価することもできる.この場合は不確定信号の
グループはなく、(i)か(iii)のいずれかに区分
けするためその分信号処理は簡単になるが境界付近のデ
ータについては判定誤差のもとになりやすい欠点もある
.しかし、これはデータ数が十分多ければ無視できるよ
うになる. さらに第14図のデータは眼球運動の様子の一端を示す
データとしても大いに検討価値がある.すなわち、どの
くらいの速度で動いていくのかの目安がつかめるし,血
管からはずれる時と戻る時の運動の比較も行なえるなど
学術的にも非常に有益な情報をもたらすと考えられる. [発明の効果] 以上説明したように、本発明によれば、光電検出信号を
所定の単位サンプリング時間ごとに光電子パルスとして
計数し、その計数値データを一測定時間内にわたって時
系列的にコンピュータのメモリに格納し、測定終了後格
納されたデータを複数のユニット時間毎に分割して各ユ
ニット時間ごとに順次光子相関関数と時間相関長τCを
求め、前記時間相関長を所定の基準値と比較することに
より測定データを分類するようにしているので、測定終
了後,再度データを読み出して分類にしたがって、例え
ば、血管からの信号か周辺組織にはずれた時の信号か、
どちらとも言えない不明確な信号か等の判別を容易に評
価することができ、正確で確実な眼科診断が可能になる
[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to an ophthalmological diagnostic method, in particular, to irradiating a laser beam of a predetermined diameter to the fundus of the eye, and forming a laser speck on an observation surface by scattered reflected light from the biological tissue of the fundus. The fluctuation of the pattern is
This paper relates to an ophthalmological detection method in which the blood flow state of the fundus tissue is measured by detecting speckle light intensity changes through a micro circular detection aperture with a predetermined diameter and determining the photon correlation function. [Prior Art] As a method for measuring vascular blood flow in tissues such as the retina by irradiating the fundus of the eye with a laser beam, there is a method known as “InvestigativeOp.
hthal+mology. Vol1. ll. No.
ll, p. 936.November 1972. “Scien
ce, Vol1. l86. Nov. 29. p. 830
.. In 1974 and other publications, JP-A-55-75668. 55
-75669. Publication No. 55-75670, Japanese Unexamined Patent Publication No. 1983
-142885 (UK 13132/76.USP
4.166.695), JP-A-56-12503
Publication No. 3 (corresponding to British (GB) 79/37799), Japanese Patent Application Publication No. 118730/1983 IUsP 4,402.
601) The laser Doppler method shown in asp4.142.796 is known. However, the Doppler method is currently difficult to put into practical use due to the complexity and precision of the optical system, the complexity of handling, and the instability and uncertainty of the measurement results. In order to solve these problems, the applicant has developed a laser speckle method (for example, Japanese Patent Laid-Open No. 60-199430.60-2032) which has already been applied to skin blood flow measurement.
35. 60-203236 publication or Optic
sLetter Vol. 10, No. 3. 198
March 5th. p. A method has been proposed in which the blood flow state of the eye tissue is evaluated by applying the method (denoted as 104, etc.) to the eye region. These are published in Japanese Patent Application Laid-Open No. 62-275431 (
USP 4.743. l07, EPC2348691,
Japanese Unexamined Patent Publication No. 63-238843 (EPC 28424
8), Japanese Patent Application Laid-open No. 63-242220 (EPC 28)
5 314). In the methods described in these publications, for example, when measuring the fundus of the eye, an image is formed on an optical Fourier transformation surface, a Fraunhofer diffraction surface, or an imaging surface (or magnified imaging surface) conjugate with the fundus. The intensity change of the time-varying speckle pattern is extracted using a detection aperture. [Problems to be Solved by the Invention] When evaluating the blood flow of a specific blood vessel, it is sufficient to detect a speckle pattern on the image plane. Regarding this, the above-mentioned Japanese Patent Application Laid-Open No. 63-242220 (E
PC 285314). In this method, a detection aperture is set above a desired blood vessel image on an enlarged image plane, and a speckle signal is obtained by extracting temporal intensity fluctuations of the image plane speckle pattern there. Therefore, if the fundus image on the detection surface shifts laterally during measurement due to various factors such as eye movement, relative positional deviation between the device and the subject's eye, misalignment, vibration, etc., the blood vessel image being measured may differ from the detection aperture. Situations often occur in which the sensor moves out of position, approaches a blood vessel wall, or another blood vessel next to it enters the detection position. This is a major problem that constantly arises in patients with diseased eyes during clinical practice, especially due to insufficient fixation or fear on the part of the examinee. Therefore, when looking at the correlation function of the signal obtained from one measurement, various components are mixed, making it impossible to measure the correct vascular blood flow stably and with good reproducibility every time. Furthermore, it is extremely difficult and impractical to remove unnecessary components from the correlation function curve data once measured and extract the original vascular blood flow signal. In other words, what ingredients are unnecessary?
This is because it is unclear to what extent it is included and contributes to the final result. Also, if blinking or instantaneous noise-free signals are introduced during measurement, the shape of the measured correlation data may be distorted, making it impossible to evaluate correctly, and one measurement may be difficult due to the mere instantaneous signals. It was a waste and I had to start over again. Therefore, the present invention has been made to solve these problems, and an object of the present invention is to provide an ophthalmologic diagnosis method that can obtain reliable correlation data values and perform accurate ophthalmologic diagnosis. 10 Steps for Solving Problems J In order to solve such problems, in the present invention, the fundus is irradiated with a laser beam of a predetermined diameter, and a laser beam is formed on the observation surface by scattered reflected light from the fundus biological tissue. In an ophthalmological diagnostic method, photoelectric detection is used to photoelectrically detect fluctuations in a laser speckle pattern as speckle light intensity changes through a detection aperture, and measure the blood flow state of the fundus tissue based on the results of measuring the photon correlation function. Detection signals are counted as photoelectron pulses at each predetermined unit sampling time, and the counted value data is stored in a computer memory in chronological order over one measurement time, and after the measurement is completed, the stored data is stored every multiple unit times. Divide into photon correlation function and time correlation length sequentially for each unit time? :C is calculated and the measured data is classified by comparing the time correlation length with a predetermined reference value. [Operation] In the embodiment of the present invention, weak optical speckles from the fundus of the eye are detected as photoelectronic pulse signals, and the values obtained by counting the time-series pulses at each predetermined sampling time are stored in the memory, and after the measurement is completed, the data is re-transmitted. The signals are read out and evaluated, and based on preset criteria, it is determined whether the signal is from a blood vessel, a signal that has strayed into the surrounding tissue, or an ambiguous signal that cannot be said to be either. A final evaluation was made. This makes it possible to evaluate different signal components individually without mixing them, and even when the fundus moves, only the signals from the blood vessels can be extracted, allowing for accurate evaluation and effective use of data without wasting it. By this discrimination, it is possible to evaluate the blood flow state of the capillary region existing in the surrounding tissue and the blood flow state of the choroid layer, making it a very effective method. [Example] The present invention will be described in detail below based on the example shown in the drawings. The present invention targets the ocular region, particularly the fundus, and will be described below using an example in which fundus blood flow is measured using a fundus camera. FIG. 1 is a schematic diagram of the entire apparatus to which the method according to the present invention is applied. For example, red He-Ne (wavelength 632.
8n■) The laser beam from the laser light source I passes through a light intensity adjustment filter 2 for adjusting the light intensity via a condenser lens 1'. Furthermore, relay lens 3,
4 to the fundus illumination optical system of the fundus camera. Further, apertures 5 and 6 are installed between the relay lenses 3 and 4, and are used to select the size and shape of the laser beam irradiation area on the fundus of the eye. Also,
There is a shutter 7 at the exit of the laser light source 1, which opens and closes as necessary. As shown in Fig. 2, the laser beam guided by the relay lens 4 is reflected by a mirror 9 installed in a part of the annular opening 8a of the ring slit 8 in the fundus illumination optical system, and a light beam for fundus observation and photography is directed to the fundus. is guided onto the same optical path that is incident on the . Therefore, the laser beam is reflected by the perforated mirror I2 via the relay lenses 10 and l1, and once focused on the cornea 13a of the eye 13 through the objective lens 13', it is then diffused into the fundus 13b. reached,
Forms an irradiation area that is wider than the blood vessel diameter. This irradiation area is illuminated by an illumination optical system used as a fundus camera to facilitate observation. This observation optical system includes an observation light source 22, a condenser lens 23, and a condenser lens 25 arranged on the same optical axis as the photographing light source 24.
.. It consists of a filter 27 and a mirror 26. Since the laser beam is placed on the same optical path as this observation photographing light beam,
Laser light can be irradiated to a desired position on the fundus 13b by using the left and right, up and down swing mechanisms and fixation guidance mechanism of the fundus camera. Incidentally, since the filter 27 disposed between the condenser lens 25 and the mirror 26 is configured as a wavelength separation filter as shown in FIG. 3, the red component contained in the observation and shadow light is cut. Speckle light generated when the laser light is scattered by blood cells moving in the fundus blood vessels is received again by the objective lens 13', passes through the perforated mirror l2, and reaches the shadow lens 14 and the wavelength separation mirror l5. This wavelength separation mirror 1
Similar to the filter 27, the filter 5 has the spectral characteristics shown in FIG. Most of the speckle light (red) generated by this is reflected. This reflected light passes through the lens 16 once and then passes through the image plane 35.
is further imaged by the objective lens 19a of the microscope optical system 19.
and is magnified through the eyepiece lens 19b. The magnified image passes through the detection aperture 20, is collected again by the condenser lens 2l, and is detected by a photomultiplier tube (photomultiplier) 40. A shutter 40' is arranged in front of the photomultiplier tube 40, and an output signal from the shutter 40' obtained when the shutter is opened is inputted to a signal processing circuit 50. This signal processing circuit 50 includes an amplifier 51 as shown in FIG.
, a photon counting unit 52, a correlator 53, a microcomputer 54, a CRT 55, a printer 56, and a memory 57. On the other hand, the light that has passed through the wavelength separation mirror l5 passes through the relay lens 28, flip-up mirror 29, mirror 30, and reticle 3.
1. It is configured so that it can be observed through an eyepiece lens 33 and photographed with a photographic film 32. In the apparatus configured as described above, first, the power is turned on, a subject is set, the fundus 13b of the subject's eye 13 is observed through the observation optical systems 22 to 26, and the laser light source 1 is activated. At this time, the output level is set to the adjustment level using the light amount adjustment filter 2, the size and shape of the laser irradiation area is set using the apertures 5 and 6, the shutter 7 is opened, and the measurement position is set, and then the observation optical system 28 Check the speckle pattern through ~31. In this embodiment, in order to facilitate laser irradiation, the laser beam irradiation area at the measurement site of the fundus 13b is set to a wider area than the blood vessel, for example,
Since it is set to 3 msφ, there may naturally be cases where a plurality of relatively large blood vessels are included in addition to capillaries. Therefore, in order to measure the blood flow of a specific blood vessel, the blood vessel image to be measured is selected on the enlarged image plane, and the detection aperture 20 is set in the image. That is, a conjugate image of the fundus is formed on the imaging plane 35 in FIG. This is magnified by the objective lens 19a and eyepiece lens 19b of the microscope optical system 19, and a detection aperture 20 is placed on the surface of the magnified image to detect changes in speckle light intensity. The detected light is collected by a condenser lens 2l and converted into a signal by a photomultiplier tube 40 (shutter 40' is open). Photomultiplier tube 4 during measurement
The output from 0 is a speckle signal that fluctuates over time as blood cells move. The speckle signal is amplified by the amplifier 5l in the signal processing circuit 50, and then sent to the photon counting unit 52.
time-series data of photoelectron pulses corresponding to the light intensity is counted at regular time intervals through the 3D controller, and the counted value is stored in the red memory 57. ? After the M determination, the data is read from the memory 57, the photon phase leap number is determined by the phase shifter 53, and the data is displayed on the CRT 55 or printer 56 along with the analysis and evaluation results.
A series of these controls is performed by a microcomputer 54. As described above, in this embodiment, the detection aperture 20 is placed on the magnified image plane, so a desired blood vessel image to be measured in the laser irradiation area is selected, and the detection aperture 20 is placed within that blood vessel image. By adjusting the position of the detection aperture 20 or the fixation of the target eye l3, the blood flow in one specific blood vessel can be measured. As the detection aperture 20, a minute circular aperture such as a bottle hole can be used effectively. For example, as shown in FIG.
When the book 60 is obtained as an enlarged image, the image plane speckle 62 inside the blood vessel fluctuates through a pinhole 6l as shown in FIG. When the speckle crosses the detection aperture 20, the detected light intensity changes and a speckle signal can be obtained. The image plane speckles 62 that are actually observed exhibit a boiling motion characteristic of speckles from a living body due to multiple scattering effects and the like. In other words, even if the blood cells flow and move in a fixed direction, the image plane speckles 62 do not move in a fixed direction according to the flow like a simple image, which is a so-called translational motion, but the individual speckles move in a fixed direction. , without changing the location, randomly flashing light and dark over time,
It has become clear that the speckle pattern as a whole is a type of motion that constantly and randomly fluctuates in intensity. However, in this case as well, the bottle hole 6l
There is no difference in the fact that irregular changes in speckle blinking can be obtained as a speckle signal. If the blood flow is faster, the speed at which the image surface speckle 62 repeatedly flashes between light and dark on the enlarged image will change faster, and the time change of the speckle signal will become faster, so the signal will have more high-frequency components. The signal processing circuit 50 calculates the autocorrelation function of the signal, and evaluates the degree of attenuation based on the correlation time. In that case, for example, if the delay time at which the correlation value becomes l/e (or l/2, etc.) is the correlation time -cc as shown in FIG. The speeds are linearly related. Since the fluctuation speed of the image plane speckle 62 directly reflects the blood flow velocity, the blood flow velocity V is determined from 1/τC.
can be evaluated from the relationship shown in Figure 8. In the signal processing circuit 50, the time-series pulse signal obtained from the photon counting unit 52 is processed as shown in FIG.
is converted into a pulse train signal with a density proportional to the intensity of the speckle signal. Storing this information one by one in memory requires a very large amount of memory, and requires a processing system with high-speed time response, which is impractical. Therefore, in this embodiment, pulses are counted as shown in FIG. 9(C) every predetermined short sampling time Δt, and the counted value is calculated as nl. n2. n3. =-ni・-n Store in memory as m. Therefore, m during one measurement time T
Sampling is performed twice, and m pieces of data are stored. In other words, T=mΔt. It is best to set Δt to a time that can be sufficiently divided and measured, with reference to the value τcmin, which is considered to be the shortest of the time correlation lengths C of the signal to be measured. For example, τcmin=2
If 0 71 sec, Δt≦0.5 ~ 1 u
Set to the value of sec. This is because Δt is the minimum time unit and determines the time resolution of the measurement. Next, Figure 10(a). As shown in (b), one measurement time T
When m pieces of data are stored with = mΔt, T f! :m
/ h equal parts, and each divided time T'=hΔt is divided into unit time Ul. U2. Let U3=Uw/h, Fig. IO (C
), the correlation function is found for each unit in sequence.
At this time, the same delay time Δτ may be set from U1 to Us/h, or the optimum Δτ may be set individually. In this way, the time resolution T' that divides I/h constant T into m/h pieces is
With hΔt, one measurement can be evaluated in a time-sharing manner. However, if T"=hΔt is too short, the correlation function of each unit will not converge sufficiently, so Δt<<T" is necessary.
Also, if the number of divisions is small and <T' is close to T, there is no meaning in time division, so at least T'<T/10 (m/h
210) conditions are preferable. At this time, the number of decompositions m/h can be changed repeatedly, and the optimal number of decompositions can be searched for. If there is clearly abnormal data such as blinking during the process, the unit containing it can be excluded from the evaluation, which is very practical clinically. The correlation function of each unit is the first! When obtained as shown in Figure O (C), the correlation time t Cl. after each smoothing. 1: C2. r.
Find c3-z cm/h. In general, in the case of image plane detection, in the case of signals from blood vessels, the speckles move quickly and τC becomes short, as shown in Figure 11, and in the case of signals from surrounding tissues, the speckles move as shown in Figure 12. late, τC
becomes longer. The threshold value of C for the blood vessel signal is set in advance as V, and the threshold value of C for the surrounding tissue signal is set as t. These data have been statistically examined from multiple human eye data to obtain approximate values. Also, if necessary, set value τV
.. t can be changed. Therefore, the τC (tecl.tec2...-τC■/h) of each unit is sequentially determined by τV and tet, and the units are divided into groups. That is, (i) τC〈
τv. (iilτV≦teC≦τt. (iiiil
Divide into three parts: tt and tc. If the average value of τC is calculated for each group after classification, the average ici in (i) is the value of the blood vessel signal, the average value in (ii) is the value of uncertain data, and the average value in (iii) is the value of the blood vessel signal. This means that, on average, ciii can be evaluated separately from the surrounding tissue signal value. In this way, even if the measurement point deviates from the blood vessel during measurement, or even if it accidentally returns to the blood vessel, we collect and evaluate only the data from when the blood vessel was being measured. Results can be evaluated well, and clinical measurements can be performed efficiently without wasting anything. Furthermore, since the data near the blood vessel wall is divided into the group (ii), it is possible to avoid evaluating the measurement data of slow blood vessels near the blood vessel wall in the group (i). On the other hand, if you want to include such a component in an overly comprehensive evaluation as (i), you can adjust the threshold value τV to a longer value. This is very practical because even data that is clearly abnormal due to blinking or noise among the measured data will not be included in (i) by the above grouping, and can be evaluated after being excluded. The data at this time (iii) may be used to evaluate the blood flow state of the capillary region and choroid.
Overall, almost no data is wasted, and evaluation is possible even if there is movement, so re-measurement is not necessary. Also the first
In Figure 3, T. Instead of calculating the average value of C, all the data of n in the units belonging to (il are joined together to form one The correlation function may be calculated and smoothed to obtain τci.
Perform the same process for (ii) and (iii) and
ii. Find τciii. Furthermore, the T Cl. for each unit obtained in FIG. c2
-... is plotted against the time axis scale as shown in FIG. 14, and the threshold value l/V. 1/τt is also displayed as a line, l/tc>1/τV11/ is a blood vessel signal, and l/τV21/tc>1
/T: By displaying t as an uncertain signal and l/τt≧l/τc as a surrounding tissue signal, for example, the 14th
It is possible to obtain a characteristic diagram similar to the one shown in the figure. Regarding the example in the same figure, it can be inferred that it detached from the blood vessel midway through and returned again. Therefore, the time-series changes shown by the measurement data can be clearly seen, which is very useful for evaluation. Also, a certain data 75 in FIG. 14 is a blood vessel signal, but if this becomes a surrounding tissue signal in a blot like data 75', this data 75 (75''
) is l/τC, ≧1 7 t: v
Therefore, it is difficult to think that only unit U2 was dislodged from the blood vessel, and it can be evaluated that correct measurement was not possible due to blinking and other unnecessary noise. In other words, it is also very useful to be able to judge and consider from Figure 14 whether or not the time-series changes in data are systematic. Also, as a special case of the above example, let ZV=zt.
rc<zv=it and zc>T. It is also possible to evaluate the results by dividing them into two groups, v = τt. In this case, there is no group of uncertain signals and the signal is divided into either (i) or (iii), which simplifies signal processing, but it also has the disadvantage that data near the boundary is likely to cause judgment errors. be. However, this can be ignored if the number of data is large enough. Furthermore, the data in Figure 14 is of great value as data that shows part of the state of eye movement. In other words, it is possible to get an idea of how fast the object is moving, and it is also possible to compare the movement when it leaves the blood vessel and when it returns, which is thought to provide extremely useful information academically. [Effects of the Invention] As explained above, according to the present invention, a photoelectric detection signal is counted as a photoelectron pulse at each predetermined unit sampling time, and the counted value data is chronologically stored in a computer over one measurement period. The data is stored in a memory, and after the measurement is completed, the stored data is divided into multiple unit times, the photon correlation function and the time correlation length τC are sequentially determined for each unit time, and the time correlation length is compared with a predetermined reference value. By doing this, the measured data is classified, so after the measurement is completed, the data is read out again and according to the classification, for example, is it a signal from a blood vessel or a signal when it is missed in the surrounding tissue?
It is possible to easily evaluate whether the signal is ambiguous or unclear, making accurate and reliable ophthalmologic diagnosis possible.

【図面の簡単な説明】[Brief explanation of the drawing]

第1図は、本発明方法が用いられる眼科装置の構成を示
した構成図,第2図は、リングスリットの構成図,第3
図は,フィルタの分光特性を示した説明図,第4図は、
信号処理装置の構成を示したブロック図,第5図は、検
出開口の面で観察される像面スペックルを示した説明図
、第6図は,検出開口の構成を示した説明図、第7図は
、遅れ時間に対する相関値を示した特性図、第8図は、
速度と相関値の関係を示した特性図、第9図(a)〜(
C)は、スペックル信号のサンプリングを説明した波形
図、第lO図(a)〜(e)は、測定時間を分割して相
関関数を演算する動作を説明した信号波形図、第11図
と第12図は,血管とその周辺組織での相関関数を示し
た特性図、第13図は,グループ分けされた時間相関長
の平均を求める状態を示した説明図、第14図は、時間
相関長の逆数を時系列的に示した特性図である. 20・・・検出開口 3 5 −−・像面 40・・・光電子増倍管 50・・・信号処理装置 53・・・相関器 54・・・マイクロコンピュータ 第7図 *M ヒ相mJt#,E,if*ile第8図 スΔ′−7フーし椹{I一諸1杉t 第9図 相関自tt,r,i怜壬躬 第11図 62イ勲免スどッフ1レ 相關馴較L承す譬寄生図 第12図 第13図 綺聞柑藺長め遵宿1ホず特l庁旧 第14図
FIG. 1 is a block diagram showing the configuration of an ophthalmological apparatus in which the method of the present invention is used, FIG. 2 is a block diagram of a ring slit, and FIG.
The figure is an explanatory diagram showing the spectral characteristics of the filter.
FIG. 5 is a block diagram showing the configuration of the signal processing device, and FIG. 5 is an explanatory diagram showing image plane speckle observed in the plane of the detection aperture. FIG. Figure 7 is a characteristic diagram showing correlation values with respect to delay time, and Figure 8 is a characteristic diagram showing correlation values with respect to delay time.
Characteristic diagrams showing the relationship between speed and correlation value, Figures 9(a) to (
C) is a waveform diagram explaining the sampling of the speckle signal, Figures 10(a) to (e) are signal waveform diagrams explaining the operation of dividing the measurement time and calculating the correlation function, and Figure 11. Figure 12 is a characteristic diagram showing the correlation function between blood vessels and surrounding tissues, Figure 13 is an explanatory diagram showing how to calculate the average of time correlation lengths divided into groups, and Figure 14 is a diagram showing the time correlation function. This is a characteristic diagram showing the reciprocal of length over time. 20...Detection aperture 3 5--Image plane 40...Photomultiplier tube 50...Signal processing device 53...Correlator 54...Microcomputer Fig. 7 *M Hyphasic mJt#, E, if * ile Fig. 8 S Δ'-7 Fushi 椹 {I 1 1 cedar t Fig. 9 Correlation tt, r, i Reimu 11 Fig. 62 Familiarization L accepted parasitic diagram Figure 12 Figure 13

Claims (1)

【特許請求の範囲】 1)眼底に所定径のレーザー光を照射し、眼底生体組織
からの散乱反射光によって観測面に形成されるレーザー
スペックルパターンの変動を、検出開口を介してスペッ
クル光強度変化として光電検出し、その光子相関関数を
測定した結果に基づいて、眼底組織の血流状態を測定す
る眼科診断方法において、 光電検出信号を所定の単位サンプリング時間ごとに光電
子パルスとして計数し、 その計数値データを一測定時間内にわたって時系列的に
コンピュータのメモリに格納し、 測定終了後格納されたデータをユニット時間毎に複数に
分割して各ユニット時間ごとに順次光子相関関数と時間
相関長τcを求め、 前記時間相関長を所定の基準値と比較することにより測
定データを分類することを特徴とする眼科診断方法。 2)前記基準値を1つあるいは2つ設けて測定データを
2種類あるいは3種類に分類するようにしたことを特徴
とする請求項第1項に記載の眼科診断方法。 3)前記順次求めた時間相関長の各逆数の値に従って血
管信号、周辺組織信号、いずれか不明の不確定信号を得
るようにしたことを特徴とする請求項第1項または第2
項に記載の眼科診断方法。 4)前記分類された測定データのグループごとにその時
間相関長の平均値を算出することを特徴とする請求項第
1項から第3項までのいずれか1項に記載の眼科診断方
法。 5)前記分類された測定データのグループごとに一つの
光子相関関数を求めることを特徴とする請求項第1項か
ら第4項までのいずれか1項に記載の眼科診断方法。
[Scope of Claims] 1) A laser beam of a predetermined diameter is irradiated to the fundus of the eye, and fluctuations in the laser speckle pattern formed on the observation surface by scattered reflected light from the biological tissues of the fundus are detected as speckle light through a detection aperture. In an ophthalmological diagnostic method that measures the blood flow state of fundus tissue based on the results of photoelectric detection as intensity changes and measurement of the photon correlation function, the photoelectric detection signal is counted as photoelectron pulses at each predetermined unit sampling time, The counted value data is stored in the computer memory in time series over one measurement time, and after the measurement is completed, the stored data is divided into multiple units of time and the photon correlation function and time correlation are sequentially calculated for each unit time. An ophthalmological diagnostic method, characterized in that the measured data is classified by determining the length τc and comparing the time correlation length with a predetermined reference value. 2) The ophthalmological diagnosis method according to claim 1, characterized in that one or two of the reference values are provided to classify the measurement data into two or three types. 3) A blood vessel signal, a surrounding tissue signal, or an unknown uncertain signal is obtained according to the value of each reciprocal of the time correlation length obtained sequentially.
Ophthalmological diagnostic methods described in Section. 4) The ophthalmological diagnosis method according to any one of claims 1 to 3, characterized in that the average value of the time correlation length is calculated for each group of the classified measurement data. 5) The ophthalmological diagnosis method according to any one of claims 1 to 4, characterized in that one photon correlation function is determined for each group of the classified measurement data.
JP1051956A 1989-03-06 1989-03-06 Ophthalmology diagnostic method Pending JPH02232030A (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP1051956A JPH02232030A (en) 1989-03-06 1989-03-06 Ophthalmology diagnostic method
EP90302101A EP0389120B1 (en) 1989-03-06 1990-02-28 Ophthalmological diagnosis method
DE69016071T DE69016071T2 (en) 1989-03-06 1990-02-28 Eye diagnostic procedures.
US07/489,284 US5116116A (en) 1989-03-06 1990-03-05 Ophthalmological diagnosis method

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
JP1051956A JPH02232030A (en) 1989-03-06 1989-03-06 Ophthalmology diagnostic method

Publications (1)

Publication Number Publication Date
JPH02232030A true JPH02232030A (en) 1990-09-14

Family

ID=12901324

Family Applications (1)

Application Number Title Priority Date Filing Date
JP1051956A Pending JPH02232030A (en) 1989-03-06 1989-03-06 Ophthalmology diagnostic method

Country Status (1)

Country Link
JP (1) JPH02232030A (en)

Cited By (2)

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WO2015167005A1 (en) * 2014-05-02 2015-11-05 興和株式会社 Image-processing device, image-processing method and image-processing program
WO2016189243A1 (en) * 2015-05-26 2016-12-01 Centre National De La Recherche Scientifique Device for detecting a state of the cornea of the eye and associated method

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2015167005A1 (en) * 2014-05-02 2015-11-05 興和株式会社 Image-processing device, image-processing method and image-processing program
JPWO2015167005A1 (en) * 2014-05-02 2017-04-20 興和株式会社 Image processing apparatus, image processing method, and image processing program
US10111582B2 (en) 2014-05-02 2018-10-30 Kowa Company, Ltd. Image processing device and method to identify disease in an ocular fundus image
WO2016189243A1 (en) * 2015-05-26 2016-12-01 Centre National De La Recherche Scientifique Device for detecting a state of the cornea of the eye and associated method
FR3036607A1 (en) * 2015-05-26 2016-12-02 Centre Nat Rech Scient DEVICE FOR DETECTING A CONDITION OF THE CORNE OF THE EYE AND ASSOCIATED METHOD

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